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Prevalence of tumor necrosis factor alpha inducing protein ( tipα) gene of Helicobacter pylori and its association with upper gastrointestinal diseases in India. 3 Biotech 2021; 11:246. [PMID: 33968589 DOI: 10.1007/s13205-021-02804-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 04/21/2021] [Indexed: 10/21/2022] Open
Abstract
Helicobacter pylori (H. pylori) is known to cause several gastroduodenal diseases including chronic Gastritis, Peptic Ulcer disease and Gastric Cancer. Virulent genes of H. pylori like cagA, vacA are known to be responsible for the disease pathogenesis. However, these virulence genes are not always found to be associated with disease outcome in all populations around the world. Tumor necrosis factor alpha inducing protein tipα is a newly discovered virulence gene of H. pylori and is an inducer of certain cytokines and chemokines that are responsible for causing stomach cancer. Therefore, we conducted a study, which aims to find the prevalence of tipα gene in the Indian patients with gastroduodenal symptoms, and its association with H. pylori related gastroduodenal diseases. 267 clinical H. pylori isolates are included in our study for finding the prevalence of tipα gene and its association with cagA and vacA gene using PCR assay. The current study shows that the prevalence rate of tipα gene is 59.9%. Our study has found a significant association (p < 0.05) of tipα gene with Non Ulcer Dyspepsia (NUD) and an association of cagA and vacAs1m1 with Gastritis and Duodenal Ulcer. Our study demonstrates for the first time the presence of tipα as virulence factor of H. pylori strain in Indian population isolated from patients suffering from gastroduodenal diseases. Further, tipα is significantly associated with NUD but not with other gastroduodenal diseases in India.
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Crowley E, Hussey S. Helicobacter pylori in Childhood. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2021:275-292.e12. [DOI: 10.1016/b978-0-323-67293-1.00027-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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da Silva FAF, de Brito BB, Santos MLC, Marques HS, Sampaio MM, da Silva Júnior RT, Apolonio JS, de Carvalho LS, Silva CS, de Sá Santos LK, Oliveira MV, Rocha GA, de Magalhães Queiroz DM, de Melo FF. Treatment of Helicobacter pylori infection in children: A systematic review. World J Meta-Anal 2020; 8:292-308. [DOI: 10.13105/wjma.v8.i4.292] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 09/03/2020] [Accepted: 09/04/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection is predominantly acquired in childhood. When indicated, the most accepted treatment for H. pylori eradication in this age group is first-line triple therapy. However, the increasing resistance to clarithromycin and nitroimidazoles has been associated with treatment failure, and thus, alternative treatment regimens have been proposed.
AIM To perform a systematic review of randomized controlled trials on treatment regimens for H. pylori infection in children.
METHODS We surveyed relevant articles published in English from 2010 to April 2020 in the PubMed and MEDLINE databases. Keywords included “Helicobacter pylori”/”children or childhood”/”treatment or eradication.” The risk of bias was evaluated according to the Cochrane Handbook of Systematic Reviews for Interventions.
RESULTS Among the 1144 records identified through the database, 20 articles were selected. Four studies compared the eradication rates of H. pylori infection between standard triple therapies, changing only the main antibiotic used. Seven studies evaluated the effectiveness of standard triple therapy with the addition of probiotics. One study investigated the relationship between the effectiveness in the eradication rates of standard triple therapy and vitamin E levels. Six studies analyzed the eradication rates of sequential therapy.
CONCLUSION The findings suggest that although standard triple therapy is the most recommended regimen for children by the current guidelines, other therapeutic schemes have shown promising results and may also be recommended for clinical practice in the future.
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Affiliation(s)
| | - Breno Bittencourt de Brito
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Maria Luísa Cordeiro Santos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Hanna Santos Marques
- Campus Vitória da Conquista, Universidade Estadual do Sudoeste da Bahia, Vitória da Conquista 45083-900, Bahia, Brazil
| | - Mariana Miranda Sampaio
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | | | - Jonathan Santos Apolonio
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Lorena Sousa de Carvalho
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Camilo Santana Silva
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Luana Kauany de Sá Santos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Márcio Vasconcelos Oliveira
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Gifone Aguiar Rocha
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Dulciene Maria de Magalhães Queiroz
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
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Kpoghomou MA, Wang J, Wang T, Jin G. Association of Helicobacter pylori babA2 gene and gastric cancer risk: a meta-analysis. BMC Cancer 2020; 20:465. [PMID: 32448131 PMCID: PMC7247142 DOI: 10.1186/s12885-020-06962-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Accepted: 05/13/2020] [Indexed: 01/06/2023] Open
Abstract
Background The association of Helicobacter pylori (H. pylori) babA2 gene with gastric cancer (GC) was reported by several studies, but results were inconsistent. This meta-analysis was performed to investigate the relationship between H. pylori babA2 gene and GC risk. Methods Case-control studies involving the association between H. pylori babA2 gene and GC risk were systematically identified from PubMed databases. A meta-analysis was used to pool studies and to estimate odds ratios (ORs) with 95% confidence intervals (CIs) of H. pylori babA2 gene associated with GC risk. Results Twenty studies were identified with a total of 1289 GC cases and 1081 controls. H. pylori babA2 gene was associated with an increased risk of GC by 2.05 fold (95% CI, 1.30–3.24, P = 0.002). In subgroup analysis, we found that H. pylori babA2 gene was significantly associated with GC risk in Asian population (OR = 2.63, 95% CI: 1.36–5.09 P = 0.004) but not in South American population (OR = 1.35, 95% CI: 0.69–2.64, P = 0.379). Conclusions This meta-analysis indicates that H. pylori babA2 gene may be associated with increased risk of GC, especially in Asian population.
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Affiliation(s)
- Marce-Amara Kpoghomou
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, 211166, China
| | - Jinchen Wang
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, 211166, China
| | - Tianpei Wang
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, 211166, China
| | - Guanfu Jin
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. .,Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, 211166, China.
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Rocha GA, de Melo FF, Cabral MMDA, de Brito BB, da Silva FAF, Queiroz DMM. Interleukin-27 is abrogated in gastric cancer, but highly expressed in other Helicobacter pylori-associated gastroduodenal diseases. Helicobacter 2020; 25:e12667. [PMID: 31702083 DOI: 10.1111/hel.12667] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 10/01/2019] [Accepted: 10/03/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND IL-27 has dual roles in the immune response either stimulating Th1 or inhibiting Th17 cells. Because there is a particular link of IL-23/Th17 axis in the development of cancer and IL-27 has been considered a potential treatment for cancer, we evaluated the gastric and serum concentrations of IL-27 in two mutually exclusive Helicobacter pylori-associated diseases, gastric cancer (GC) and duodenal ulcer (DU). MATERIAL AND METHODS We prospectively studied 110 H pylori-positive patients and 40 healthy blood donors. Serum and gastric concentrations of IL-27 and cytokines of the Th1/Th17 cells were assessed by ELISA. RESULTS IL-27 was not detected in GC patients, but the cytokine concentration was very high in the patients with DU. IL-27 was also detected in the gastritis patients and in the H pylori-positive blood donors. IL27RA mRNA expression in peripheral blood mononuclear cells, evaluated by rt-PCR, was stimulated by H pylori strains. The cytokine concentration positively correlated with the Th1 and negatively with Th17 cell representative cytokine levels. Gastric IL-27 concentrations were positively correlated with increased degree of mononuclear and polymorphonuclear cells on the antral gastric mucosa of DU patients in consonance with the DU gastritis pattern. IL-12p70 and IFN-γ gastric concentrations were significantly higher in DU than in GC. Conversely, gastric concentrations of Th17 cell-associated cytokines (IL-1β, IL-6, IL-17A, IL-23, and TGF-β) were significantly higher in GC than in DU patients. CONCLUSION Although H pylori infection is able to elicit IL-27 and IL-27Rα secretion, DU and GC have diametrically opposed cytokine patterns.
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Affiliation(s)
- Gifone A Rocha
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Fabrício F de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Brazil
| | - Mônica M D A Cabral
- Department of Pathology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Breno B de Brito
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Brazil
| | | | - Dulciene M M Queiroz
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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Oliveira de Lima VC, de Araújo Machado RJ, Vieira Monteiro NK, de Lyra IL, da Silva Camillo C, Coelho Serquiz A, Silva de Oliveira A, da Silva Rufino FP, Leal Lima Maciel B, Ferreira Uchôa A, Antunes dos Santos E, de Araújo Morais AH. Gastroprotective and antielastase effects of protein inhibitors from Erythrina velutina seeds in an experimental ulcer model. Biochem Cell Biol 2017; 95:243-250. [DOI: 10.1139/bcb-2016-0034] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Trypsin and chymotrypsin inhibitors from Erythrina velutina seeds have been previously isolated by our group. In previous studies using a sepsis model, we demonstrated the antitumor and anti-inflammatory action of these compounds. This study aimed to evaluate the gastroprotective and antielastase effects of protein inhibitors from E. velutina seeds in an experimental stress-induced ulcer model. Two protein isolates from E. velutina seeds, with antitrypsin (PIAT) and antichymotrypsin (PIAQ) activities, were tested. Both protein isolates showed a high affinity and inhibitory effect against human neutrophil elastase, with 84% and 85% inhibition, respectively. Gastric ulcer was induced using ethanol (99%) in 6 groups of animals (female Wistar rats, n = 6). Before ulcer induction, these animals were treated for 5 days with one of the following: (1) PIAT (0.2 mg·kg−1), (2) PIAT (0.4 mg·kg−1), (3) PIAQ (0.035 mg·kg−1), (4) ranitidine hydrochloride (50 mg·kg−1), (5) saline solution (0.9%), or (6) no intervention (sham). Both PIAT and PIAQ protected gastric mucosa, preventing hemorrhagic lesions, edema, and mucus loss. No histologic toxic effects of PIAT or PIAQ were seen in liver and pancreatic cells. Our results show that protein isolates from E. velutina seeds have potential gastroprotective effects, placing these compounds as natural candidates for gastric ulcer prevention.
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Affiliation(s)
| | | | | | - Ibson Lucas de Lyra
- Biochemistry Department, Biosciences Center, Federal University of Rio Grande do Norte, 59078-970 Natal, RN, Brazil
| | - Christina da Silva Camillo
- Morphology Department, Biosciences Center, Federal University of Rio Grande do Norte, 59078-970 Natal, RN, Brazil
| | - Alexandre Coelho Serquiz
- Biochemistry Department, Biosciences Center, Federal University of Rio Grande do Norte, 59078-970 Natal, RN, Brazil
| | - Adeliana Silva de Oliveira
- Biochemistry Department, Biosciences Center, Federal University of Rio Grande do Norte, 59078-970 Natal, RN, Brazil
| | | | - Bruna Leal Lima Maciel
- Nutrition Department Center for Health Sciences, Federal University of Rio Grande do Norte, 59078-970 Natal, RN, Brazil
| | - Adriana Ferreira Uchôa
- Molecular Biology and Genetics Department, Center for Health Sciences, Federal University of Rio Grande do Norte, 59078-970 Natal, RN, Brazil
| | - Elizeu Antunes dos Santos
- Biochemistry Department, Biosciences Center, Federal University of Rio Grande do Norte, 59078-970 Natal, RN, Brazil
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Vinagre IDF, Queiroz ALD, Silva Júnior MRD, Vinagre RMDF, Martins LC. HELICOBACTER PYLORI INFECTION IN PATIENTS WITH DIFFERENT GASTROINTESTINAL DISEASES FROM NORTHERN BRAZIL. ARQUIVOS DE GASTROENTEROLOGIA 2016; 52:266-71. [PMID: 26840466 DOI: 10.1590/s0004-28032015000400004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/21/2015] [Accepted: 06/18/2015] [Indexed: 01/23/2023]
Abstract
BACKGROUND The mechanisms whereby Helicobacter pylori produces different pathological manifestations in the stomach and duodenum are not fully understood. Considering the geographic diversity in the prevalence of virulence factors of this microorganism and their association with the development of different diseases, the search for pathogenicity markers such as CagA and VacA alleles by molecular techniques has intensified. OBJECTIVES To investigate the presence of H. pylori infection and the frequency of different genotypes of this bacterium in patients with gastrointestinal diseases from Northern Brazil, and to establish their association with the histopathological findings. METHODS In a prospective study, samples were collected from 554 patients with different gastrointestinal diseases (gastritis, duodenal ulcer, gastric ulcer, and gastric cancer) seen at a referral hospital attending the entire State of Pará, located in the metropolitan region of Belém. Data such as gender and age obtained with an epidemiological questionnaire were analyzed. The presence of H. pylori and the bacterial genotype were investigated by PCR. Gastric biopsies were assessed histologically. RESULTS The prevalence of H. pylori infection was 91%. Infection was more frequent among patients with gastric ulcer and gastric cancer. In these groups, there was a predominance of men and older patients when compared to the other two groups studied. The predominant bacterial genotype was s1m1cagA+, which was more frequent among patients with gastric ulcer, duodenal ulcer and gastric cancer. A significant association was observed between s1m1cagA+ strains and a higher degree of inflammation, neutrophil activity and development of intestinal metaplasia. CONCLUSION The present study demonstrates a high incidence of H. pylori infection in the patients analyzed, especially among those with gastric ulcer and gastric cancer. Virulent s1m1cagA+ strains predominated and were associated with more severe lesions.
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Ghosh P, Sarkar A, Ganguly M, Raghwan, Alam J, De R, Mukhopadhyay AK. Helicobacter pylori strains harboring babA2 from Indian sub population are associated with increased virulence in ex vivo study. Gut Pathog 2016; 8:1. [PMID: 26759607 PMCID: PMC4709984 DOI: 10.1186/s13099-015-0083-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Accepted: 12/23/2015] [Indexed: 12/13/2022] Open
Abstract
Background The babA2 gene along with the cagA and vacA of Helicobacter pylori has been considered as a risk factor for the disease outcome in certain populations. This study was aimed to understand the role of babA2 of H. pylori with the background of cagA and vacA in disease manifestations in Indian sub population. Methods A total of 114 H. pylori strains isolated from duodenal ulcer (DU) (n = 53) and non-ulcer dyspepsia (NUD) patients (n = 61) were
screened for the prevalence of these virulence markers by PCR. The comparative study of IL-8 production and apoptosis were done by co-culturing the AGS cell line with H. pylori strains with different genotypes. Adherence assay was performed with babA2 positive and negative strains. Two isogenic mutants of babA2 were constructed and the aforesaid comparative studies were carried out. Results PCR results indicated that 90.6 % (48/53), 82 % (50/61) and 73.6 % (39/53) strains from DU patients were positive for cagA, vacA, and babA2, respectively. Whereas the prevalence of these genes in NUD subjects were 70.5 % (43/61); 69.8 % (37/53), and 65.6 % (39/61), respectively. Although adherence to AGS cells was comparable among strains with babA2 positive and negative genotypes, but the triple positive strains could induce highest degree of IL-8 production and apoptosis, followed by the cagA−/vacA−/babA2+ strains and triple negative strains, respectively. The wild type strains showed significantly higher IL-8 induction as well as apoptosis in ex vivo than its isogenic mutant of babA2. Conclusion PCR study demonstrated that there was no significant association between the distribution of babA2 genotype or of triple positive strains and disease outcome in this sub population. The adherence assay showed that there was no significant difference in the extent of adherence to AGS cells among babA2 positive and negative strains. But the ex vivo study indicated that the triple positive or even the babA2 only positive strains are involved in increased virulence. The wild type strains also exhibited increased virulence compared to the babA2 mutant strains. This inconsistency demonstrated that bacterial genotype along with host genetic polymorphisms or other factors play important role in determining the clinical manifestation of H. pylori infections.
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Affiliation(s)
- Prachetash Ghosh
- Division of Bacteriology, National Institute of Cholera & Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India
| | - Avijit Sarkar
- Division of Bacteriology, National Institute of Cholera & Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India
| | - Mou Ganguly
- Division of Bacteriology, National Institute of Cholera & Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India
| | - Raghwan
- Division of Bacteriology, National Institute of Cholera & Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India
| | - Jawed Alam
- Division of Bacteriology, National Institute of Cholera & Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India
| | - Ronita De
- Division of Bacteriology, National Institute of Cholera & Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India
| | - Asish K Mukhopadhyay
- Division of Bacteriology, National Institute of Cholera & Enteric Diseases, P 33, CIT Road, Scheme XM, Beliaghata, Kolkata, 700010 India
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Oliveira JGD, Ferreira CHT, Camerin ACS, Rota CA, Meurer L, Silveira TRD. Prevalence of infection with cagA-positive Helicobacter pylori strains among children and adolescents in southern Brazil. ARQUIVOS DE GASTROENTEROLOGIA 2015; 51:180-5. [PMID: 25296076 DOI: 10.1590/s0004-28032014000300003] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2013] [Accepted: 01/13/2014] [Indexed: 12/16/2022]
Abstract
CONTEXT Helicobacter pylori (H. pylori) has a worldwide distribution, but the prevalence of infection, virulence factors, and clinical presentation vary widely according to the studied population. In Brazil, a continental country composed of several ethnicities and cultural habits, the behavior of infection also appears to vary, as many other studies have shown. OBJECTIVES Describe the prevalence of infection with cagA-positive H. pylori strains in a group of children and adolescents who underwent esophagogastroduodenoscopy in Porto Alegre, Rio Grande do Sul. METHODS Fifty-four gastric biopsy specimens of children and adolescents with H. pylori infection demonstrated by histology, urease test and molecular analysis were tested for the presence of cagA positive H. pylori strains by the polymerase chain reaction method. RESULTS The prevalence of cagA-positive H. pylori was 29.6% (95% confidence interval, 18 to 43.6%). There were no statistically significant differences in clinical or demographic characteristics or in the endoscopic and histological features of patients infected with cagA-positive strains as compared with those infected by cagA-negative strains. CONCLUSIONS he study showed a low prevalence of infection with cagA-positive H. pylori strains among children and adolescents who underwent EGD in southern Brazil, in comparison to studies conducted with children from other regions of Brazil. There was no association between the presence of cagA-positive strains and more severe clinical presentations in the studied sample.
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Affiliation(s)
- Juliana Ghisleni de Oliveira
- Programa de Pós Graduação em Saúde da Criança e do Adolescente, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brasil
| | - Cristina Helena Targa Ferreira
- Programa de Pós Graduação em Saúde da Criança e do Adolescente, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brasil
| | | | - Cláudia Augustin Rota
- Programa de Pós Graduação em Saúde da Criança e do Adolescente, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brasil
| | - Luíse Meurer
- Departamento de Patologia, Hospital de Clínicas de Porto Alegre e Medicina Digital, Porto Alegre, RS, Brasil
| | - Themis Reverbel da Silveira
- Programa de Pós Graduação em Saúde da Criança e do Adolescente, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brasil
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Bontems P, Aksoy E, Burette A, Segers V, Deprez C, Mascart F, Cadranel S. NF-κB activation and severity of gastritis in Helicobacter pylori-infected children and adults. Helicobacter 2014; 19:157-67. [PMID: 24661597 DOI: 10.1111/hel.12118] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND In contrast to adults, Helicobacter pylori gastritis in children is reported as milder and ulcer disease as uncommon, but unequivocal data are lacking. OBJECTIVES To compare the frequency of gastro-duodenal ulcers in children and adults as well as the proportion of Helicobacter pylori infection in these patients and to study the effect of chronological age on NF-κB activation and on severity of gastritis. DESIGN Patients referred in one pediatric and one adult facility for upper GI endoscopy were included. Gastric biopsies were obtained in consecutive Helicobacter pylori-infected patients and age-matched negative controls for immunohistochemistry and electrophoresis mobility shift assay. Three age groups were defined: younger than 8 years, 8-17 years, and adults. RESULTS Peptic ulcer disease was less frequent in children and less frequently associated with Helicobacter pylori infection. When comparing infected subjects to controls, densities of neutrophils and CD20 cells in the lamina propria increased in all age groups, CD3 cells increasing only in patients older than 8 years and CD8 cells only in adults. NF-κB-p65-positive cells were also increased only in infected adults as well as NF-κB-binding activity. A positive correlation was found between age and densities of neutrophils and CD3, but not of CD8 or CD20 cells. CONCLUSION Peptic ulcer disease was less frequent in children and less frequently caused by Helicobacter pylori infection. The different clinical outcome of the infection in children can be the consequence of the lower mucosal immune response.
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Affiliation(s)
- Patrick Bontems
- Paediatric Gastroenterology-Hepatology, Queen Fabiola Children's University Hospital, Université Libre de Bruxelles, Av JJ Crocq 15, 1020, Brussels, Belgium; Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium
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Ozbey G, Dogan Y, Demiroren K. Prevalence of Helicobacter pylori virulence genotypes among children in Eastern Turkey. World J Gastroenterol 2013; 19:6585-6589. [PMID: 24151385 PMCID: PMC3801372 DOI: 10.3748/wjg.v19.i39.6585] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2013] [Revised: 08/15/2013] [Accepted: 08/20/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify the virulence genotypes of Helicobacter pylori (H. pylori) if present in children in Eastern Turkey and if those genotypes are mostly associated with severe clinical presentations.
METHODS: A total of 49 H. pylori positive Turkish children (42 with antral nodularity and 7 with peptic ulcer) who underwent upper gastrointestinal endoscopy with abdominal symptoms during the period from March 2011 to September 2012 were enrolled in this study. Antral nodularity was diagnosed endoscopically by two of the authors. We determined for the presence of cagA, vacA, cagE, iceA and babA2 genotypes of H. pylori isolates in DNA obtained directly from frozen gastric biopsy samples by polymerase chain reaction test using specific primers.
RESULTS: Of the 49 H. pylori isolates studied, 61.2%, 91.8%, 22.4%, 28.6%, 57.1% and 40.8% were positive for the cagA, vacA s1, cagE, iceA1, iceA2 and babA2 genes, respectively. We showed that the most common vacA subtype was s1a (79.6%). However, the s2 gene was found less frequently with an isolation rate of 8.2% of the H. pylori isolates. The genotypes iceA2 and vacA s1m2 were the most frequently found types in children with antral nodularity. In addition, the genotypes iceA1, babA2 and vacA s1m1 were found in similar ratios in all the H. pylori isolates obtained from children with peptic ulcer. The genotypes vacA s2m1 and s1c were not observed in any of isolates studied.
CONCLUSION: This study showed that vacA s1m2, cagA and iceA2 were the most common genotypes, and no association between antral nodularity and genotypes was observed.
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Rafeey M, Ghotaslou R, Milani M, Farokhi N, Ghojazadeh M. Abstracts of the Academy of Breastfeeding Medicine 18th Annual International Meeting. Philadelphia, Pennsylvania, USA. November 21-24, 2013. Breastfeed Med 2013; 8 Suppl:S2-22. [PMID: 24188181 DOI: 10.1089/bfm.2013.9982] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
| | | | | | - Nima Farokhi
- Tabriz University of Medical Sciences, Tabriz, Iran
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Khedmat H, Karami A, Safiri Z, Amini M, Bakhtiari A, Karbasi A, Jayhounian M, Jalalian H, Taheri S. Helicobacter pylori genotypes can predict gastric tissue histopathology: a longitudinal study of Iranian patients. J Infect Public Health 2012; 5:153-8. [PMID: 22541262 DOI: 10.1016/j.jiph.2011.10.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2011] [Revised: 08/22/2011] [Accepted: 10/10/2011] [Indexed: 01/25/2023] Open
Abstract
INTRODUCTION Several factors have been suggested to account for differences in the virulence of Helicobacter pylori infections in various populations. Evidence suggests the existence of different strains of H. pylori with different degrees of virulence. The present study aimed to investigate the gastric histopathology in Iranian patients infected with H. pylori and to investigate the relationship between the severity of gastritis and four different bacterial virulence-associated genotypes. METHODS AND MATERIALS All of the patients with positive results from a pathological examination, a rapid urease test, and PCR analysis for H. pylori infection were consecutively included into the study. The classification and grading of gastritis were performed according to the Sydney System. Esophagitis was classified endoscopically according to the Savary-Miller grading system. The primers used in this study targeted 16S rRNa (521 bp), Urease A (411 bp), Cag A (400 bp), and 26 kDa (303 bp). RESULTS Twenty-eight patients were included in the study. The presence of Cag A showed a significant relationship with higher gastritis grades (3.0±0.7 vs. 2.3±0.9, p=0.024) and higher scores for H. pylori infection (3.0±0.7 vs. 2.3±0.7, p=0.027). The patients infected with 26 kDa-positive H. pylori had significantly higher infection scores (3.5±0.6 vs. 2.5±0.6, p=0.020). CONCLUSION This study showed that CagA-positive H. pylori infection is associated with more severe gastritis and with increased bacterial density and inflammation in the biopsy specimens. The 303-bp positive genotype was also significantly associated with higher grades of esophagitis. Additional in-depth trials will be helpful in extending our findings.
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Affiliation(s)
- Hossein Khedmat
- Baqiyatallah Research Center for Gastroenterology & Liver Diseases, Tehran, Iran.
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Hussey S, Jones NL. Helicobacter pylori in Childhood. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2011:293-308.e10. [DOI: 10.1016/b978-1-4377-0774-8.10028-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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High prevalence of clarithromycin resistance and cagA, vacA, iceA2, and babA2 genotypes of Helicobacter pylori in Brazilian children. J Clin Microbiol 2010; 48:4266-8. [PMID: 20826649 DOI: 10.1128/jcm.01034-10] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
We isolated 45 Helicobacter pylori strains from 217 child patients. Resistance to clarithromycin, metronidazole, amoxicillin, and tetracycline was detected in 27%, 13%, 4%, and 0% of strains, respectively. The A2143G mutation was the most prevalent (67%) among clarithromycin-resistant strains. In addition, strain genotyping revealed a significant association between gastritis severity and the simultaneous presence of cagA, vacA s1m1, iceA2, and babA2 genes.
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In situ expression of cagA and risk of gastroduodenal disease in Helicobacter pylori-infected children. J Pediatr Gastroenterol Nutr 2010; 50:167-72. [PMID: 20038850 PMCID: PMC2824336 DOI: 10.1097/mpg.0b013e3181bab326] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIM Gastroduodenal disease is more common among adults and children with cagA+ Helicobacter pylori infection, but disease severity varies among those infected with cagA+ strains. We examined whether cagA in situ expression can predict disease manifestations among H pylori-infected children. PATIENTS AND METHODS Fifty-one children were selected from 805 patients with abdominal symptoms who underwent esophagogastroduodenoscopy with gastric biopsies. Endoscopic and histologic gastritis were scored and H pylori colonization was quantified by Genta stain and in situ hybridization expression of 16S rRNA and cagA. RESULTS Endoscopy was either normal (n = 14) or demonstrated nodularity (n = 18), gastric ulcer (n = 8) or duodenal ulcer (n = 11). H pylori was present in 7, 18, 6, and 10 children, respectively. Expression of 16S rRNA and cagA were significantly higher in children with ulcer compared with normal children. The fraction of H pylori bacteria expressing cagA in situ was higher in children with ulcer compared to those with endoscopic nodularity (P < 0.05). CONCLUSIONS Thus, cagA in situ expression is increased in H pylori-infected children with peptic ulcers and may play a role in the pathogenesis of peptic ulcer disease during childhood. Determination of in situ expression of cagA complements traditional isolation and in vitro testing of single-colony isolates.
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Frequency of Helicobacter pylori vacA genotypes in Iranian patients with gastric and duodenal ulcer. J Infect Public Health 2009; 2:204-8. [PMID: 20701884 DOI: 10.1016/j.jiph.2009.08.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2009] [Revised: 08/07/2009] [Accepted: 08/27/2009] [Indexed: 11/21/2022] Open
Abstract
Helicobacter pylori infection is a risk factor for developing chronic peptic ulcers and gastric cancer. The purpose of this study was to investigate the frequency of Helicobacter pylori vacA genotypes in patients with gastric and duodenal ulcer. A total of 100 biopsy specimens of patients with gastric (n=50) and duodenal (n=50) ulcer were collected. The specimens were cultured on selective media and incubated in a microaerophilic atmosphere at 37 degrees C for 5-10 days. The isolates were characterized to species level by conventional biochemical tests. The extracted DNA from isolates was used to perform a polymerase chain reaction based, simultaneous analysis of the cagA status, allelic variation of the signal regions (s1, s2) and the middle regions (m1, m2) of the vacA gene. H. pylori isolated from 50 specimens of patients and the vacA gene was detected in all isolates. Among vacA genotypes the s1/m1 was the most common in H. pylori isolates from patients with gastric ulcer (56%) and duodenal ulcer (68%). This study demonstrated that vacA slml is common genotype of H. pylori in patients with peptic ulcer and the vacA allele s1 of this bacterium is associated with ulcer.
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Abstract
BACKGROUND Helicobacter pylori infection rates in duodenal ulcer (DU) patients may be lower than previously estimated. AIM To review the real prevalence of H. pylori-negative DUs and its possible causes. METHODS Bibliographical searches in MEDLINE looking for the terms 'H. pylori' and 'duodenal ulcer'. RESULTS Mean prevalence of H. pylori infection in DU disease, calculated from studies published during the last 10 years including a total of 16 080 patients, was 81%, and this figure was lower (77%) when only the last 5 years were considered. Associations with H. pylori-negative DU were: (1) False negative results of diagnostic methods, (2) NSAID use (21% in studies with <90% infection rate), (3) Complicated DU (bleeding, obstruction, perforation), (4) Smoking, (5) Isolated H. pylori duodenal colonization, (6) Older age, (7) Gastric hypersecretion, (8) Diseases of the duodenal mucosa, (9) Helicobacter'heilmanii' infection and (10) Concomitant diseases. CONCLUSION In patients with H. pylori-negative DU disease, one should carefully confirm that the assessment of H. pylori status is reliable. In truly H. pylori-negative patients, the most common single cause of DU is, by far, the use of NSAIDs. Ulcers not associated with H. pylori, NSAIDs or other obvious causes should, for the present, be viewed as 'idiopathic'. True idiopathic DU disease only exceptionally exists.
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Affiliation(s)
- J P Gisbert
- Gastroenterology Unit, Hospital Universitario de la Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)m, Madrid, Spain.
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Prevalence and clinical relevance of cagA, vacA, and iceA genotypes of Helicobacter pylori isolated from Slovenian children. J Pediatr Gastroenterol Nutr 2009; 49:289-96. [PMID: 19525870 DOI: 10.1097/mpg.0b013e31818f09f2] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Although infection with Helicobacter pylori in children mostly induces asymptomatic chronic gastritis, the clinical outcome of H pylori infection is generally unpredictable. To identify the risk subgroup of infected children who can progress toward serious gastrointestinal disease, we assessed the prevalence of H pylori virulence genes cagA, vacA, and iceA in children from southeastern Europe and correlated their presence with the severity of histological changes in the stomach. MATERIALS AND METHODS A total of 165 children (age range 4-18 years, mean 13 years) with H pylori infection were studied for a 6-year period. Virulence genes were determined by polymerase chain reaction from biopsy samples. RESULTS The cagA gene was present in 61.2% of patients. The predominant vacA genotype was s1m1 (42%), followed by s1m2 (28%), and s2m2 (24%). IceA genotypes iceA1 and iceA2 were detected in 62% and 31% of the samples, respectively. Multiple genotypes were found in 11.5% of isolates. The H pylori density score, the degree of chronic and acute inflammation, correlated with a cagA-positive status (P < 0.01, P < 0.01, P = 0.01, respectively). Higher bacterial infiltration (P < 0.01) and degree of chronic inflammation (P = 0.03) were detected in vacA s1-positive samples. CONCLUSION CagA, vacA s1m1, and iceA1 genotypes are the predominant genotypes of H pylori isolated from the southeastern European pediatric population. CagA and vacA s1 are important virulence determinants of H pylori in children, but were not found associated with an increased incidence of precancerous gastric lesions.
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Cartágenes VD, Martins LC, Carneiro LM, Barile KADS, Corvelo TC. Helicobacter pylori em crianças e associação de cepas CagA na transmissão mãe-filho na Amazônia brasileira. Rev Soc Bras Med Trop 2009; 42:298-302. [DOI: 10.1590/s0037-86822009000300011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2009] [Accepted: 05/12/2009] [Indexed: 01/16/2023] Open
Abstract
Investigou-se a prevalência de infecção pela Helicobacter pylori em amostras de sangue de 100 crianças de 1 a 12 anos e de suas mães através dos métodos de hemaglutinação indireta e anti-CagA pelo ensaio ELISA. Destas 100 crianças, foram obtidas 79 amostras de fezes e realizada pesquisa de antígenos da bactéria nas fezes por ELISA de captura. Os antígenos foram detectados em 54,4% (43/79) das crianças, e os anticorpos no soro em 43% (34/79), métodos que apresentaram desempenhos semelhantes, com maiores discordâncias nas crianças de 1 a 4 anos. A soroprevalência nas crianças foi de 50% (50/100) e nas mães de 86% (86/100). Mães infectadas representaram fator de risco 19 vezes superior ao de mães soronegativas para determinar infecção em seus filhos (p < 0,05), sobretudo as mães com cepas CagA+ (p < 0,05). O contato direto pessoa-pessoa pode ser um modo de transmissão desta infecção.
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Silva DG, Stevens RH, Macedo JMB, Albano RM, Falabella MEV, Veerman ECI, Tinoco EMB. Detection of cytotoxin genotypes of Helicobacter pylori in stomach, saliva and dental plaque. Arch Oral Biol 2009; 54:684-8. [PMID: 19442963 DOI: 10.1016/j.archoralbio.2009.04.006] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2009] [Revised: 03/31/2009] [Accepted: 04/13/2009] [Indexed: 12/13/2022]
Abstract
BACKGROUND The aim of this study was to detect the presence of Helicobacter pylori and its virulent cagA genes in the oral cavity of individuals with upper gastric diseases. Sixty-two individuals (42+/-2.3 years) with dispepsy symptoms, referred for gastroscopy and who were H. pylori positive in the gastric biopsy, were recruited and separated in two groups: case group-individuals with gastric disease (n = 30); control group-individuals with no gastric disease (n = 32); saliva, dental plaque and biopsy samples were collected from all individuals. Oral and biopsy samples were analyzed by PCR using specific primers for H. pylori 16S ribosomal and cagA genes. PCR products were sequenced for DNA homology confirmation. H. pylori was detected neither in dental plaque nor in saliva in the control group. In the case group H. pylori DNA was detected in 16/30 (53.3%) saliva samples and in 11/30 (36.6%) dental plaque samples. The cagA gene was detected in 13/30 (43.3%) gastric biopsies, in 7/16 (43.8%) saliva samples, and in 3/11 (27.3%) dental plaque samples. Eighteen (60.0%) individuals in the case group were H. pylori positive both in oral and biopsy samples, and 8 (26.6%) of those were positive for cagA-H. pylori DNA. H. pylori and its virulent clone showed a higher prevalence in the oral cavity of individuals in the case group than in the control group (p < 0.05). Our results suggest that dental plaque and saliva may serve as temporary reservoir for H. pylori and its virulent cagA variant in individuals with gastric disease.
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Affiliation(s)
- Denise G Silva
- Escola de Odontologia, UNIGRANRIO, Duque de Caxias, Brazil.
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Pediatric Helicobacter pylori isolates display distinct gene coding capacities and virulence gene marker profiles. J Clin Microbiol 2009; 47:1680-8. [PMID: 19386830 DOI: 10.1128/jcm.00273-09] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori strains display remarkable genetic diversity, and the presence of strains bearing the toxigenic vacA s1 allele, a complete cag pathogenicity island (PAI), cagA alleles containing multiple EPIYA phosphorylation sites, and expressing the BabA adhesin correlates with development of gastroduodenal disease in adults. To better understand the genetic variability present among pediatric strains and its relationship to disease, we characterized H. pylori strains infecting 47 pediatric North American patients. Prevalence of mixed infection was assessed by random amplified polymorphic DNA analysis of multiple H. pylori clones from each patient. Microarray-based comparative genomic hybridization was used to examine the genomic content of the pediatric strains. The cagA and vacA alleles were further characterized by allele-specific PCR. A range of EPIYA motif configurations were observed for the cagA gene, which was present in strains from 22 patients (47%), but only 19 (41%) patients contained a complete cag PAI. Thirty patients (64%) were infected with a strain having the vacA s1 allele, and 28 patients (60%) had the babA gene. The presence of a functional cag PAI was correlated with ulcer disease (P = 0.0095). In spite of declining rates of H. pylori infection in North America, at least 11% of patients had mixed infection. Pediatric strains differ in their spectrum of strain-variable genes and percentage of absent genes in comparison to adult strains. Most children were infected with H. pylori strains lacking the cag PAI, but the presence of a complete cag PAI, in contrast to other virulence markers, was associated with more severe gastroduodenal disease.
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Proença-Modena JL, Acrani GO, Brocchi M. Helicobacter pylori: phenotypes, genotypes and virulence genes. Future Microbiol 2009; 4:223-40. [PMID: 19257848 DOI: 10.2217/17460913.4.2.223] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Helicobacter pylori is a Gram-negative, microaerophilic bacterium that colonizes the gastric mucus overlying the epithelium of the stomach in more than 50% of the world's population. This gastric colonization induces chronic gastric inflammation in all infected individuals, but only induces clinical diseases in 10-20% of infected individuals. These include peptic ulcers, acute and atrophic gastritis, intestinal metaplasia, gastric adenocarcinoma and gastric B-cell lymphoma. Various bacterial virulence factors are associated with the development of such gastric diseases, and the characterization of these markers could aid medical prognosis, which could be extremely important in predicting clinical outcomes. The purpose of this review is to summarize the role of the phenotypes, virulence-related genes and genotypes of H. pylori in the establishment of gastric colonization and the development of associated diseases.
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Affiliation(s)
- José Luiz Proença-Modena
- Department of Cell & Molecular Biology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
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Moura SB, Almeida LR, Guerra JB, Rocha GA, Camargos Rocha AM, Melo FF, Corrêa-Oliveira R, Bittencourt P, Carvalho SD, Magalhães Queiroz DM. Toll-like receptor (TLR2, TLR4 and TLR5) gene polymorphisms and Helicobacter pylori infection in children with and without duodenal ulcer. Microbes Infect 2008; 10:1477-83. [PMID: 18809506 DOI: 10.1016/j.micinf.2008.08.009] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2008] [Revised: 08/22/2008] [Accepted: 08/27/2008] [Indexed: 12/31/2022]
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Gomes LI, Rocha GA, Rocha AMC, Soares TF, Oliveira CA, Bittencourt PFS, Queiroz DMM. Lack of association between Helicobacter pylori infection with dupA-positive strains and gastroduodenal diseases in Brazilian patients. Int J Med Microbiol 2007; 298:223-30. [PMID: 17897881 DOI: 10.1016/j.ijmm.2007.05.006] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2006] [Revised: 04/27/2007] [Accepted: 05/29/2007] [Indexed: 12/16/2022] Open
Abstract
Duodenal ulcer-promoting gene (dupA) was recently described as a new putative Helicobacter pylori virulence marker associated with an increased risk for duodenal ulcer and reduced risk for gastric carcinoma in Japan and Korea. Since differences regarding the association among H. pylori markers and H. pylori-associated diseases have been demonstrated around the world, we evaluated the presence of the gene in 482 strains from Brazilian children (34 with duodenal ulcer and 97 with gastritis) and adults (126 with duodenal ulcer, 144 with gastritis and 81 with gastric carcinoma) by PCR using the described primers and an additional set of primers based on Brazilian strain sequences. The results were confirmed by sequencing. The presence of cagA was investigated by PCR and also included in the analysis. dupA was present in 445 (92.32%) and absent in 29 (6.02%) strains. All samples from children with and without duodenal ulcer were dupA-positive (p=1.0). No association was observed among the strains from adults with gastritis (92.36%), duodenal ulcer (87.30%, p=0.30) and gastric carcinoma (87.65%, p=0.31). Conversely, cagA-positve status remained independently associated with duodenal ulcer (children: odds ratios (OR)=5.58, 95% confidence intervals (CI)=1.67-18.50; adults: OR=3.33, 95% CI=2.14-5.19) and gastric carcinoma (OR=6.58, 95% CI=3.51-12.30) in multivariate analyses. The presence of dupA was significantly higher in strains from children than in those from adults (p=0.01). In conclusion, dupA is highly frequent and not associated with H. pylori-associated diseases in both Brazilian adults and children, which points to regional differences in the distribution of the gene.
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Affiliation(s)
- Luciana I Gomes
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190/4026, CEP 30130-100, Belo Horizonte, MG, Brazil
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Yang YJ, Wu JJ, Sheu BS, Chen CR, Lu CC, Yang HB. Helicobacter pylori infection can change the intensity of gastric Lewis antigen expressions differently between adults and children. J Biomed Sci 2007; 15:29-36. [PMID: 17710564 DOI: 10.1007/s11373-007-9202-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2007] [Accepted: 08/01/2007] [Indexed: 12/21/2022] Open
Abstract
This study tested whether there were different expressions of gastric Lewis antigens between children and adults with Helicobacter pylori infection, and whether the difference was related to the infection outcome. About 68 dyspeptic children and 110 dyspeptic adults were enrolled to check H. pylori infection, its colonization density, and the related histology. Gastric Lewis antigens b (Le(b)), x (Le(x)), and sialyl-Lewis x (sialyl-Le(x)) were immunohistochemically stained and scored for the intensity. The H. pylori-infected adults, but not the children, had a lower Le(b) intensity over the antrum (p=0.019) but higher Le(b) intensity over the corpus (p=0.001) than the non-infected ones. Over the antrum, both the H. pylori-infected children and adults had a lower Le(x) and higher sialyl-Le(x) intensity than those non-infected ones (p<0.05). The H. pylori-infected adults had a higher bacterial density (p=0.004) and Le(b) intensity (p=0.016) over the corpus than the H. pylori-infected children. For the H. pylori-infected adults, but not children, the corpus had a higher Le(b) (p=0.038) and lower Le(x) (p=0.005) intensity than the antrum. Furthermore, the H. pylori-infected adults expressed a higher Le(b) and had a higher bacterial density than those with weak Le(b) (antrum, p<0.001; corpus, p=0.001). In conclusion, H. pylori infection is associated with the intensity change of Lewis antigen expressions in the stomach. The changes of gastric Lewis antigen expressions are different between adults and children with H. pylori infection, which may exert different H. pylori colonization over the corpus between adults and children.
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Affiliation(s)
- Yao-Jong Yang
- Department of Pediatrics, National Cheng Kung University, Tainan, Taiwan
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Erzin Y, Koksal V, Altun S, Dobrucali A, Aslan M, Erdamar S, Dirican A, Kocazeybek B. Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA, babA2 genotypes and correlation with clinical outcome in Turkish patients with dyspepsia. Helicobacter 2006; 11:574-80. [PMID: 17083380 DOI: 10.1111/j.1523-5378.2006.00461.x] [Citation(s) in RCA: 86] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Distinct virulence factors of Helicobacter pylori have been associated with clinical outcome of the infection; however, considerable variations have been reported from different geographic regions and data on genotypes of Turkish H. pylori isolates are sparse. AIM To determine the prevalence of specific genotypes of H. pylori in Turkish patients with dyspepsia. MATERIALS AND METHODS Ninety-three H. pylori-positive patients [30 with non-ulcer dyspepsia (NUD), 30 with duodenal ulcer (DU), and 33 with gastric cancer (GC)] who were admitted to our endoscopy unit due to dyspepsia were enrolled in the study. H. pylori infection was confirmed in all patients by histology and rapid urease test (RUT). The presence of vacA alleles, cagA, cagE, iceA, and babA2 genotypes were determined by polymerase chain reaction (PCR). Chi-squared test and Fisher's exact test were used for statistical comparisons and multivariate regression analysis was performed to find out independent predictors of different clinical outcomes. RESULTS Turkish strains examined predominantly possessed the vacA s1,m2 (48.4%) and s1,m1 (40.7%) genotypes. The vacA s1a genotype was detected in 66.7, 96.4, and 87.9% of isolates from patients with NUD, DU, and GC, respectively, and its presence was significantly associated with that of DU (p = .004), GC (p = .043), and cagA gene (p = .021). None of the cases was found to harbor the s1c genotype. The frequencies of the cagA and cagE genes among studied isolates were 73.6 and 59.3%, respectively. The cagA gene was significantly associated with the presence of DU (p = .004) and GC (p = .003), and the cagE gene, too, was significantly associated with the presence of DU (p = .002) and GC (p = .000). All H. pylori isolates possessed the iceA gene. In all, 68 isolates (74.7%) were positive for iceA1 and 23 (25.3%) for iceA2. The frequency of icea1 gene was significantly higher in cases with GC (85%) than in cases with NUD (60%) (p = .026). The frequency of babA2 gene was 23.3, 46.4, and 87.9% in isolates of patients with NUD, DU, and GC, respectively. When compared to cases with NUD (p = .000) and DU (p = .000), the presence of babA2 gene was significantly higher in cases with GC. Multivariate regression analysis disclosed cagE (p = .006) and vacA s1a (p = .027) genotypes to be independent predictors of DU and babA2 (p = .000) and cagE (p = .013) genotypes to be independent predictors of GC. CONCLUSIONS H. pylori vacA s1a, cagA, cagE genotypes have significant relations with the presence of DU and GC, and iceA1, babA2 with GC in Turkish patients with dyspepsia, whereas cagE and vacA s1a genotypes are independent predictors of DU, and babA2 and cagE genotypes are independent predictors of GC.
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Affiliation(s)
- Y Erzin
- Department of Gastroenterology, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey
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Lopes AIC, Palha A, Monteiro L, Olcastro M, Pelerito A, Fernandes A. Helicobacter pylori genotypes in children from a population at high gastric cancer risk: no association with gastroduodenal histopathology. Am J Gastroenterol 2006; 101:2113-22. [PMID: 16848806 DOI: 10.1111/j.1572-0241.2006.00732.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Both bacterial and host determinants underlying differences in histopathology and clinical outcome in H. pylori pediatric infection, as compared to adults, are still poorly documented. Pediatric studies may provide important insights on H. pylori infection immunopathogenesis, particularly in high gastric cancer risk populations. The present study concerns H. pylori genotypic diversity of isolates in children from a population with high gastric cancer risk, and its association with demographic and clinical variables, including gastroduodenal endoscopic and histopathological features. METHODS A total of 119 subjects (mean age 10.3 yr, 1.5-18.0 yr) with H. pylori infection were studied. H. pylori vacA, cagA, and iceA genotypes were determined (PCR) in antral-obtained primary cultures; histopathological evaluation was performed in corpus, antrum, and duodenum biopsy specimens. RESULTS cagA-, vacA s2m2, and iceA2 were the most prevalent genotypes. No association was observed between H. pylori genotypes and subject demographic and clinical variables, with the exception of a significant association between vacA s2 genotype and lower corpus inflammation score (p< 0.03). CONCLUSIONS In this pediatric cohort, H. pylori genotype profiles were distinct from those reported in adult subjects in the same area, with a lower prevalence of the putative more virulent genotypes. Moreover, they were not associated with clinical expression of gastroduodenal disease, suggesting the potential role of host and/or environmental factors for the development of clinical disease at a later age.
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Affiliation(s)
- Ana Isabel Costa Lopes
- Gastroenterology Unit, Paediatric Department, University Hospital Santa Maria, Lisboa, Portugal
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Queiroz DMM, Bittencourt P, Guerra JB, Rocha AMC, Rocha GA, Carvalho AST. IL1RN polymorphism and cagA-positive Helicobacter pylori strains increase the risk of duodenal ulcer in children. Pediatr Res 2005; 58:892-6. [PMID: 16183821 DOI: 10.1203/01.pdr.0000181380.14230.8b] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Duodenal ulcers in children are associated with Helicobacter pylori gastric infection with cagA-positive strains, but factors linked to the host are poorly known. The authors evaluated the role of proinflammatory interleukin-1 gene cluster polymorphisms in the pathogenesis of duodenal ulcer. They studied prospectively 437 children 1 to years old, 209 of whom were H. pylori positive and 228 of whom were H. pylori negative. IL1B-511-C/T, -31T/C, and IL1RN Variable number of tandem repeats were genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism, PCR with confronting two-pair primers, and PCR, respectively. cagA status was evaluated by PCR. The role of the proinflammatory cytokine genotypes in the genesis of duodenal ulcer was evaluated before and after stratification of H. pylori status on logistic regression models. In the group of children without duodenal ulcer, no association was observed between H. pylori status and proinflammatory polymorphisms. Furthermore, no association between IL1 cluster genotypes and cagA status was seen in the H. pylori-positive children. However, increasing age, male sex, and IL1RN*2 were independently associated with duodenal ulcer. After stratification, in the H. pylori-positive children, increasing age, male sex, the presence of ILRN*2 allele, and cagA-positive status were independently associated with duodenal ulcer. The risk for the development of duodenal ulcer increased when a combined association of the presence of IL1RN*2 allele and infection by a cagA-positive H. pylori strain was the variable. This study provides evidence supporting independent roles of IL1RN*2 allele and cagA-positive status in the genesis of duodenal ulcer in children.
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Janulaityte-Gunther D, Kucinskiene R, Kupcinskas L, Pavilonis A, Labanauskas L, Cizauskas A, Schmidt U, Wadström T, Andersen LP. The humoral immuneresponse to Helicobacter pylori infection in children with gastrointestinal symptoms. ACTA ACUST UNITED AC 2005; 44:205-12. [PMID: 15866217 DOI: 10.1016/j.femsim.2005.02.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2004] [Revised: 02/14/2005] [Accepted: 02/15/2005] [Indexed: 02/08/2023]
Abstract
The prevalence of Helicobacter pylori is high in Eastern Europe. The purpose of this study was to estimate the prevalence of H. pylori in symptomatic Lithuanian children and to identify the infection by clinicopathological and serological analyses. One hundred sixteen symptomatic children (age 8-16) with gastritis and duodenal ulcer were included. Biopsies were histologically assessed according to the Sydney-System. Serum IgG antibodies against H. pylori were detected by an enzyme-linked immunosorbent assay (ELISA), using low molecular mass antigen. The western blot technique was used to detect serum antibodies against the cytotoxin-associated protein (CagA) using whole cell antigen. Histologically the prevalence of H. pylori infection was 79% and not influenced by demographic factors. Mucosal inflammation and atrophy were associated with a H. pylori infection. Intestinal metaplasia was found in eight children, suggesting early H. pylori acquisition in life. Increased levels of IgG antibodies were detected in 57% of children. The prevalence of IgG antibodies was significantly higher in patients with duodenal ulcer compared to children with gastritis. Forty-four (67%) H. pylori-seropositive children had antibodies against CagA. Low molecular weight-ELISA and whole cell-western blot results were significantly associated with histopathology, the presence of duodenal ulcer and the CagA status. A high number of false seronegative cases were due to poor immunological responses in children and poor locally validated tests. The prevalence of H. pylori infection in Lithuanian children is higher compared to Western Europe. The infection is acquired in early life. Diagnosing H. pylori infection, serology is helpful, but endoscopy/histology remains as gold standard.
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Soares TF, Rocha GA, Rocha AMC, Corrêa-Oliveira R, Martins-Filho OA, Carvalho AST, Bittencourt P, Oliveira CA, Faria AMC, Queiroz DMM. Phenotypic study of peripheral blood lymphocytes and humoral immune response in Helicobacter pylori infection according to age. Scand J Immunol 2005; 62:63-70. [PMID: 16091125 DOI: 10.1111/j.1365-3083.2005.01638.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
There are differences between children and adults in certain aspects of the Helicobacter pylori (HP) infection, among them the lower titre of IgG antibodies anti-HP in the former group. Thus, we investigated by means of flow cytometry CD4+/CD3+ (CD4+T), CD8+/CD3+ (CD8+T) and CD19+/CD3- (B) cells, activation/co-stimulatory markers (CD4+/HLA-DR+, CD4+/CD28+, CD8+/HLA-DR+ and CD8+/CD28+) and by means of ELISA IgG anti-HP antibodies in the peripheral blood from HP-positive and -negative children and adults. An increased CD4+/CD28+ and CD8+/CD28+ percentage and number of CD4+/CD3+ cells were seen in infected adults. Conversely, no difference was observed between infected and noninfected children, but when they were stratified by age, an increased CD4+/CD28+ cell percentage was seen in the HP-positive group older than 10 years. The mean level of IgG anti-HP was lower in younger infected children, increased with age and correlated with CD4+ cells. Our data suggest that the immune response to HP infection vary according to the age. Low percentage of activated CD4+ cell may contribute to the lower level of serum IgG anti-HP observed in younger infected children. In addition, the CD4+ cell participation during the infection seems to begin after 10 years old, when the immune response becomes similar to that seen in adults.
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Affiliation(s)
- T F Soares
- Laboratory of Research in Bacteriology, Universidade Federal de Minas Gerals, Belo Horizonte, Brazil
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Nogueira AM, Marques T, Soares PCM, David L, Reis CA, Serpa J, Queiroz DM, Rocha GA, Rocha AC. Lewis antigen expression in gastric mucosa of children: relationship with Helicobacter pylori infection. J Pediatr Gastroenterol Nutr 2004; 38:85-91. [PMID: 14676601 DOI: 10.1097/00005176-200401000-00019] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
OBJECTIVE Lewis epithelial antigen expression has a role in Helicobacter pylori adherence, presumably mainly in cagA-positive strains. The authors investigated whether Lewis antigen expression in children's gastric mucosa was associated with H. pylori infection, cagA status, patient age, or presence of duodenal ulcer (DU). METHODS The expression of Lewis A (Le(a)), B (Le(b)), X (Le(x)), and Y (Le(y)) was detected by immunohistochemistry in the antral and oxyntic mucosae of 70 children. Children were divided in four age groups (<4 years; 4-8 years; 9-12 years; and 13-18 years). RESULTS Forty-seven of the 70 children had H. pylori and 17 had DU. The cagA status was determined by polymerase chain reaction in 34 patients. Le(a) and Le(b) were expressed in 64% and 44% of the patients, respectively; Le(x) and Le(y) were expressed in the glands in all of the patients and in the superficial epithelium. Le(b) expression was more common among patients without H. pylori (15/23, 65%) than in those with H. pylori (16/47, 34%) (P = 0.03). In noninfected patients, Le(b) and superficial Le(y) expression were associated with increased age. Le(b) expression was more common in patients with chronic gastritis than in those with DU. Le(x) superficial expression was significantly associated with DU in patients with H. pylori. CONCLUSION In children, the expression of Le(b) and Le(y) in the superficial gastric epithelium depends on age. Other receptors, such as Le(x), may have a role in H. pylori colonization, especially in patients with DU. Studies assessing the expression of Lewis antigens in children may contribute to an understanding of the mechanisms of acquisition of H. pylori infection.
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Camorlinga-Ponce M, Aviles-Jimenez F, Cabrera L, Hernández-Pando R, Muñoz O, Soza J, Torres J. Intensity of inflammation, density of colonization and interleukin-8 response in the gastric mucosa of children infected with Helicobacter pylori. Helicobacter 2003; 8:554-60. [PMID: 14536002 DOI: 10.1046/j.1523-5378.2003.00176.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Few reports exist on inflammation and interleukin (IL)-8 response in H. pylori-infected children. The aim of this study was to determine the intensity of inflammation, density of colonization and magnitude of IL-8 response in children with and without H. pylori infection. MATERIALS AND METHODS We studied 45 children with dyspeptic symptoms, 21 infected with H. pylori and 24 without infection. Antrum and corpus gastric biopsies were obtained and studied for H. pylori infection with an immunofluorescence technique and for IL-8 with an immunohistochemical assay. Biopsy specimens were stained with hematoxilin and eosin and gastritis was graded according to the Sydney system. The magnitudes of the IL-8 response and H. pylori colonization were estimated microscopically with image analyzer software. RESULTS In H. pylori-infected children, mild mono-nuclear cell infiltration was found in 50%, and no neutrophils in 40% of cases. In the antrum but not in the corpus, the intensity of colonization correlated with neutrophil and mononuclear cell infiltration. The IL-8 response was significantly higher in the antrum (p <.05) and corpus (p <.02) of infected children, and was localized mainly in the surface and crypts of the epithelium. No correlation was found between the magnitude of the IL-8 response and the infiltration of either neutrophil or mononuclear cells. CONCLUSIONS In H. pylori-infected children, poor mononuclear and neutrophil infiltration was observed. Infection was associated with a higher IL-8 response by gastric epithelial cells. The density of colonization but not the IL-8 response correlated with neutrophil cell infiltration.
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Affiliation(s)
- Margarita Camorlinga-Ponce
- Unidad de Investigación Médica en Enfermedades Infecciosas, Instituto Nacional de la Nutrición Salvador Subirán, Mexico
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Oliveira AG, Santos A, Guerra JB, Rocha GA, Rocha AMC, Oliveira CA, Cabral MMDA, Nogueira AMMF, Queiroz DMM. babA2- and cagA-positive Helicobacter pylori strains are associated with duodenal ulcer and gastric carcinoma in Brazil. J Clin Microbiol 2003; 41:3964-6. [PMID: 12904430 PMCID: PMC179833 DOI: 10.1128/jcm.41.8.3964-3966.2003] [Citation(s) in RCA: 62] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The babA2 and cagA genes were investigated in 208 Brazilian Helicobacter pylori strains. A strong association between babA2 and duodenal ulcer or gastric carcinoma was observed, even after adjusting for confounding factors, such as age, gender, and cagA status. cagA-positive strains were also independently associated with H. pylori-related diseases.
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Affiliation(s)
- Adriana Gonçalves Oliveira
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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Saltik IN, Demir H, Engin D, Ertunç OD, Akyön Y, Koçak N. The cagA status of Helicobacter pylori isolates from dyspeptic children in Turkey. FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY 2003; 36:147-9. [PMID: 12738384 DOI: 10.1016/s0928-8244(03)00024-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
There are inconsistent reports regarding cytotoxin-associated gene A (cagA) status of Helicobacter pylori isolates and the severity of the mucosal lesions in children. The aim of this study was to determine the prevalence of cagA(+) strains and to evaluate its correlation with clinic and endoscopic findings. We examined 45 H. pylori strains that were grown on brain-heart infusion agar supplemented with 7% horse blood. Following 72 h of incubation colonies were harvested and bacterial DNA was extracted. Polymerase chain reaction primers F1 and B1 were used to amplify a 348-bp internal fragment of cagA. The prevalence of cagA in Turkish pediatric patients was 55.6%. No association was found between cagA status and the severity of gastro-duodenal lesions.
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Affiliation(s)
- Inci Nur Saltik
- Department of Pediatrics, Section of Gastroenterology, Hacettepe University, Faculty of Medicine, 06100 Ankara, Turkey.
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Santos A, Queiroz DMM, Ménard A, Marais A, Rocha GA, Oliveira CA, Nogueira AMMF, Uzeda M, Mégraud F. New pathogenicity marker found in the plasticity region of the Helicobacter pylori genome. J Clin Microbiol 2003; 41:1651-5. [PMID: 12682156 PMCID: PMC153914 DOI: 10.1128/jcm.41.4.1651-1655.2003] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Comparison of gastric carcinoma and gastritis isolates showed the presence of genes, probably carcinoma associated (JHP947 and JHP940), that are situated in a Helicobacter pylori genome region (45 kb in J99 and 68 kb in 26695) called the "plasticity region." This region presents a great variability of DNA sequences. We investigated, by PCR, the presence of the JHP940 and JHP947 genes, as well as the presence of a third gene which seems to be associated with gastritis (HP986), on H. pylori strains isolated from 200 Brazilian patients, 79 of whom had gastric carcinomas and 53 of whom had duodenal ulcers, to confirm this association. Gastritis isolates (n = 68) were included as a control. We also evaluated if these genes were related to the virulence-associated cagA genotype. The present methodology did not permit definitive conclusions to be reached regarding the association between the JHP940 gene and gastric carcinoma or between the HP986 gene and gastritis. However, we showed that the JHP947 gene might be implicated in the development of both duodenal ulcer and gastric carcinoma. The presence of the JHP947 gene was associated with the cagA-positive genotype. The JHP947 gene is a novel virulence marker candidate of H. pylori.
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Affiliation(s)
- Adriana Santos
- Laboratoire de Bactériologie, Université Victor Segalen Bordeaux 2, France
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Oleastro M, Gerhard M, Lopes AI, Ramalho P, Cabral J, Sousa Guerreiro A, Monteiro L. Helicobacter pylori virulence genotypes in Portuguese children and adults with gastroduodenal pathology. Eur J Clin Microbiol Infect Dis 2003; 22:85-91. [PMID: 12627281 DOI: 10.1007/s10096-002-0865-3] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The aim of this study was to evaluate the prevalence of virulence genotypes, namely cagA, vacA and babA2, of Helicobacter pylori strains isolated from Portuguese adults and children presenting gastroduodenal pathology. One hundred thirty-six strains were studied, 82 isolated from adult patients (50 with nonulcerative gastritis and 32 with active peptic ulcer) and 58 isolated from children (54 with nonulcerative gastritis and 4 with duodenal ulcer). Genotyping of cagA, vacA and babA2 was assessed by polymerase chain reaction. Overall, Helicobacter pylori strains carrying more virulent genotypes were much more prevalent in adults than in children, particularly the type I ( vacAs1- and cagA-positive) and the triple-positive ( vacAs1-, cagA- and babA2-positive) strains ( P<0.001). A subpopulation of adults and children with nonulcerative gastritis was also studied, and differences in the prevalence of virulent genotypes were observed, either for individual genotypes ( P=0.017 for cagA, P=0.010 for vacAs1) or in combinations, i.e. the type I genotype ( P=0.005) and the triple-positive strains ( P=0.031). There was no difference between the two populations in the distribution of babA2 and m1/m2 genotypes. Considering the cohort effect in the epidemiology of Helicobacter pylori infection, these results suggest that different strains might circulate during different periods of time, or that, after infection in childhood, individual strains will undergo changes during the course of infection.
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Affiliation(s)
- M Oleastro
- Laboratório de Bacteriologia, Instituto Nacional Saúde Dr Ricardo Jorge, Av Padre Cruz, 1649-016, Lisboa, Portugal.
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Dzierzanowska-Fangrat K, Crabtree JE, Rozynek E, Dura W, Celiñska-Cedro D, Wojda U, Dzierzanowska D. Helicobacter pylori cagA genotype and density of colonization in relation to gastric inflammation in children. Eur J Gastroenterol Hepatol 2002; 14:1303-7. [PMID: 12468949 DOI: 10.1097/00042737-200212000-00003] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE To assess the relationship between density determined by quantitative culture, status, and gastric histology in children. METHODS Children with clinical symptoms indicating pathology in the upper gastrointestinal tract were referred for endoscopy. From each child blood was taken for serology, and antral biopsies were obtained for quantitative culture of and histology. Histological assessment was performed according to the updated Sydney System. The status of cultured was determined by polymerase chain reaction (PCR) and serum IgG response to CagA by western blotting. RESULTS Adequate antral biopsies were obtained from 41 children with positive cultures. CagA IgG antibodies were found in 27 patients (66%), 25 of whom were also positive by the PCR. Two children infected with + strains as determined by the PCR were CagA seronegative. Infection with + strains was associated with significantly higher activity of inflammation and denser bacterial colonization in the antrum compared to negative strains. No correlation was observed between the density of colonization and chronic antral inflammation. CONCLUSIONS This study shows that infection of children with + strains of is associated with enhanced activity of antral inflammation and higher density of colonization. There is a good correlation between serum western blot and bacterial PCR positivity in determining status and a positive relationship between histology and quantitative culture in assessing density in paediatric patients.
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Affiliation(s)
- Katarzyna Dzierzanowska-Fangrat
- Department of Clinical Microbiology and Immunology, Children's Memorial Health Institute, Aleja Dzieci Polskich 20, 04-736 Warsaw, Poland
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Benenson S, Halle D, Rudensky B, Faber J, Schlesinger Y, Branski D, Rabinowitz N, Wilschanski M. Helicobacter pylori genotypes in Israeli children: the significance of geography. J Pediatr Gastroenterol Nutr 2002; 35:680-4. [PMID: 12454586 DOI: 10.1097/00005176-200211000-00018] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND There is substantial genetic variation among different isolates of Helicobacter pylori, which may affect the clinical outcome. The aims of this study were to find the common H. pylori genotypes in Israeli children and to look for a possible genotype-phenotype correlation. METHODS Ninety-eight H. pylori cultures were isolated from antral biopsy specimens of symptomatic Israeli children and were analyzed for vacA and iceA genotype and cagA and cagE status by polymerase chain reaction. RESULTS cagA and cagE genes were present in only 25.5% and 24.5%, respectively. The common vacA genotype was s2m2, which was found in 65%. Eleven specimens (11%) contained multiple vacA genotypes. iceA1 was found in 37% and iceA2 in 52% of cases. Both iceA alleles were found in 11%. Increased prevalence of iceA1 and cagE were observed in children with duodenal disease, although it did not reach significance. CONCLUSIONS The low prevalence of cagA and the high prevalence of vacA genotype s2m2 in Israeli pediatric patients are different from the genotype prevalence reported globally. However, similar findings have been reported in Egypt, indicating a possible geographic influence. There is a possible correlation between duodenal ulcer and cag E and ice A1 genotype, but the power of the study was too low to prove it.
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Affiliation(s)
- Shmuel Benenson
- Department of Medicine, Shaare Zedek Medical Center, Jerusalem, Israel
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Martins LC, Corvelo TCDO, Oti HT, Barile KADS. [Seroprevalence of antibodies against Helicobacter pylori CagA antigen in patients with gastric ulcer in the North region of Brazil]. Rev Soc Bras Med Trop 2002; 35:307-10. [PMID: 12170324 DOI: 10.1590/s0037-86822002000400005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Helicobacter pylori is a pathogenic agent with a worldwide distribution and is involved in the development of many gastrointestinal diseases. Nowadays infection with the virulent strain CagA+ of H. pylori is considered one of the main etiological factors in the development of gastric ulcer. Based on this information, we investigated the seroprevalence of virulent strains among patients with gastric ulcer from one region, using serologic tests to detect antibodies against H. pylori and CagA protein. Infection by the virulent strain was found in 82% (40/55) of the patients, and among these, 89% (40/45) presented an increased degree of inflammation in the gastric mucosa, with a dense infiltration of leukocytes in the tissue, which probably favored the formation of gastric ulcer. We concluded that the presence of the virulent strain is related to the development of an increased inflammation in the gastric mucosa.
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Affiliation(s)
- Luisa Caricio Martins
- Laboratório de Imunogenética, Departamento de Genética, Universidade Federal do Pará, Belém, PA.
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Luzza F, Pensabene L, Imeneo M, Mancuso M, Giancotti L, La Vecchia AM, Costa MC, Strisciuglio P, Pallone F. Antral nodularity and positive CagA serology are distinct and relevant markers of severe gastric inflammation in children with Helicobacter pylori infection. Helicobacter 2002; 7:46-52. [PMID: 11886473 DOI: 10.1046/j.1523-5378.2002.00055.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND The aim of this study was to assess whether the endoscopic finding of antral nodularity and serum IgG antibodies to CagA are associated with higher grades of gastric inflammation. MATERIALS AND METHODS The comprehensive data of two previously published trials were reanalysed. One hundred and fifty-three children (median age 9.5 years) who underwent gastroscopy were included. Biopsy specimens from the antrum and corpus were taken to assess Helicobacter pylori status, gastritis score and lymphoid follicles. During endoscopy, antral nodularity was noted. Serum samples were assayed for IgG antibodies to CagA. RESULTS The presence of antral nodularity (nod+) and positive CagA serology (CagA+) were each found in 32 of the 77 (41.5%) children who had evidence of H. pylori infection. Cross tabulation showed that 20 children (26%) were nod+/CagA+, 12 (15.5%) nod+/CagA-, 12 (15.5%) nod-/CagA+ and 33 (43%) nod-/CagA-. Gastritis score was significantly lower in nod-/CagA- children than in nod+/CagA- (p =.004), nod-/CagA+ (p =.002) and nod+/CagA+ (p <.001), both in the antrum and corpus. Completely normal gastric histology was only found in the nod-/CagA- subgroup of H. pylori-infected children (eight of 33, 24%). Regression analysis showed that antral nodularity and positive CagA serology were related to severe gastric inflammation independently of each other and age. Separate analysis showed that inflammation (p <.001), activity (p <.001) and H. pylori density (p =.002) scores were significantly lower in nod-/CagA- children compared with nod+/CagA+ children. The number of lymphoid follicles in the gastric mucosa was related to antral nodularity (p =.003) and positive CagA serology (p =.043), independently of each other. CONCLUSIONS Antral nodularity and positive CagA serology are distinct and relevant markers of severe gastric inflammation in children with H. pylori infection. The lack of both findings in the same child reflects low-grade or no gastritis.
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Affiliation(s)
- Francesco Luzza
- Dipartimento di Medicina Sperimentale e Clinica, Cattedra di Gastroenterologia, Università di Catanzaro 'Magna Graecia', Catanzaro, Italy
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Abstract
The dynamics of gastritis remain a topic of intense investigation. The results of these investigations have increased our knowledge concerning the development of preneoplastic lesions and cancer of the stomach and given us insight with regard to the interactions among bacterial colonization, chronic inflammation, and carcinogenesis in other organs. The past year has presented us with further data showing that the progression of chronic gastritis to gland loss and gastric cancer is related to the severity of inflammation, which is influenced by the characteristics of the bacterial strain, host genetics, and hypochlorhydria. In contrast, Helicobacter pylori eradication leads to a rapid disappearance of neutrophils in the gastric mucosa. Chronic inflammation with mononuclear cells also improves upon eradication, but at a much slower rate, usually not leading to normalization within the first year after therapy. Whether H. pylori eradication can thus prevent new development of atrophy and metaplasia as well, or lead to regression of pre-existing lesions, has been the topic of many studies by now. Unfortunately, most of these studies have suffered from their case design, limited sample size, and short follow-up. Therefore, the conflict in outcome of these case studies comes as no surprise. The few prospective, randomized, controlled studies, however, strongly confirm that H. pylori eradication leads to healing of gastritis, which can at least halt further development of atrophy and metaplasia. Whether these lesions can truly regress remains to be proven.
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Affiliation(s)
- E J Kuipers
- Department of Gastroenterology and Hepatology, Academic Hospital Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
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Gotteland M, Corvalan A, Sarmiento F, Chavez E, Backouse C, Palma M, Kakarieka E, Vial MT, Figueroa G. Gastric permeability is not increased in children colonized by CagA-positive strains of Helicobacter pylori. Dig Liver Dis 2001; 33:750-4. [PMID: 11838609 DOI: 10.1016/s1590-8658(01)80691-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Sucrose permeability has been used as a marker to detect gastric lesions in children. As CagA status of Helicobacter pylori is an important factor in determining the evolution of the gastric lesion, CagA-positive strains being more frequently associated with severe mucosal lesions, the aim of this study was to determine the prevalence of CagA-positive strains in Helicobacter pylori-colonized children and to evaluate whether the sucrose permeability test might discriminate between colonization by CagA-positive or negative strains. PATIENTS AND METHODS A series of 38 children (11.1+/-3.6 years) who required upper endoscopy for diagnostic purposes were included in the study. Endoscopy was carried out after the sucrose permeability test, and gastric biopsies were obtained for histologic examination, Helicobacter pylori detection by Giemsa staining and CLO-test, and determination of CagA status of the colonizing Helicobacter pylori strains by polymerase chain reaction. RESULTS Helicobacter pylori was detected in 26 subjects (68.4%) and of these, 16 (61.5%) were colonized by CagA-positive strains. The intensity of the histologic findings was significantly associated with the presence of Helicobacter pylori and with CagA status of the infecting strains (chi2=21.2, p=0.0017). However no significant difference in the urinary excretion of sucrose between children not colonized and children with CagA- negative or positive strains was observed (0.027% [0.012-0.035%]; 0.027% [0.016-0.047%] and 0.026% [0.016-0.038], median [range], respectively; Kruskal-Wallis analysis of variance F=0.75, p=0.69). CONCLUSIONS These results indicate that in Chile, about 60% of the Helicobacter pylori infected children are colonized by CagA-positive strains, in association with more intense lesions of the gastric mucosa, but that gastric permeability to sucrose does not discriminate between colonization by CagA-negative and positive strains of Helicobacter pylori.
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Affiliation(s)
- M Gotteland
- Gastroenterology Unit, Institute of Nutrition and Food Technology, University of Chile, Santiago.
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Rocha GA, Rocha AM, de Magalhães Queiroz M, Nogueira Mendes E, Nogueira AM, Teles de Carvalho AS. Validation of a commercial enzyme-linked immunosorbent assay to detect anti-CagA antibodies in children with Helicobacter pylori infection. J Pediatr Gastroenterol Nutr 2001; 33:515-8. [PMID: 11698776 DOI: 10.1097/00005176-200110000-00021] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Affiliation(s)
- G A Rocha
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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Abstract
BACKGROUND In spite of the worldwide distribution of Helicobacter pylori infection, recent data have reported an increased rate of non-H. pylori, non-NSAIDs-duodenal ulcer disease in adults. The estimated rate of these ulcers in children is unknown. We aimed to investigate the prevalence of non-H. pylori, non-NSAIDs-peptic ulcer disease in our pediatric patients who undergo upper endoscopic procedures. METHODS A retrospective analysis of 622 upper endoscopic reports was performed. Reports that documented mucosal ulcerations were included in our study. The demographic, clinical, endoscopic, and histological data were retrieved. The H. pylori-negative, duodenal/gastric ulcer-positive patients were compared with H. pylori-positive, duodenal/gastric ulcer-positive patients. RESULTS Out of the 622 upper endoscopy reports, a total of 11 (1.8%) children with mucosal ulceration were studied. Mucosal ulceration was distributed in the following locations: stomach-3 (27%), and duodenal bulb-10 (91%) (two children had ulcers in both the stomach and duodenal bulb). Helicobacter pylori infection was only detected in three (27%) children with duodenal ulcer. Gastritis was more severe in patients with H. pylori infection/duodenal ulcer compared with H. pylori-negative/duodenal ulcer group. No statistical difference in clinical symptoms or endoscopic appearance was observed between the H. pylori-negative and H. pylori-positive groups. CONCLUSION 'Idiopathic' (H. pylori-negative, NSAIDs-negative) duodenal/gastric ulcers are present in symptomatic children. Clinical or endoscopic characteristics are insufficient markers to identify those 'idiopathic' ulcers. Investigating the 'risk factors' for those ulcers will be helpful in reducing the morbidity in these children.
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Affiliation(s)
- Y Elitsur
- Department of Pediatrics, Division of Gastroenterology, Marshall University School of Medicine, Huntington, WV 25701-0195, USA
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Abstract
Helicobacter pylori is a bacterium that colonizes the human stomach, especially during childhood. Although it has been studied intensively during the past decade, many controversies still exist on many important issues, including the clinical relevance of virulence factors, indications for treatment, recommended procedures for diagnosis and the typical symptom profile, among others. The lack of double-blind, placebo-controlled studies in children illustrates the paucity of hard scientific data, and is the major reason for differences in opinion. Therefore, the present review of literature published during the past 2 years raises many questions.
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Affiliation(s)
- Y Vandenplas
- Academic Children's Hospital, Free University of Brussels, Brussels, Belgium.
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Ashour AA, Collares GB, Mendes EN, de Gusmão VR, Queiroz DM, Magalhães PP, de Carvalho AS, de Oliveira CA, Nogueira AM, Rocha GA, Rocha AM. iceA genotypes of Helicobacter pylori strains isolated from Brazilian children and adults. J Clin Microbiol 2001; 39:1746-50. [PMID: 11325984 PMCID: PMC88019 DOI: 10.1128/jcm.39.5.1746-1750.2001] [Citation(s) in RCA: 46] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Data concerning the geographic distribution of iceA alleles are scarce, and information on the association of the gene with the disease is rare and still controversial. Furthermore, no such study has been developed in Brazil, where duodenal ulcer and gastric adenocarcinoma are very common. We investigated, by PCR, the frequency of iceA alleles and cagA status in Helicobacter pylori strains isolated from 142 patients (62 children and 80 adults; 66 female; mean age, 30.0 years; age range, 3 to 78 years) with gastritis, duodenal ulcer, or gastric adenocarcinoma. iceA was identified in bacterium samples obtained from all patients. Eleven (7.7%) of them were infected with multiple strains. Among the patients with nonmixed infection, iceA2 allele was detected in 118 (90.1%). iceA2 allele was associated with ulcer (P = 0.02) and with carcinoma (P = 0.001). iceA2 amplicons of 229, 334, or 549 bp were detected, but none of them was associated with the patient's disorder. iceA2 strains were more frequent in patients older than 7 years (P = 0.001). The gene was also more frequent in strains obtained from males (P = 0.02). cagA was more common in strains obtained from carcinoma (P = 0.0008) and ulcer patients (P < 0.006). cagA-positive strains were more frequent in children older than 7 years (P < 0.003). No association between cagA status and sex was found (P = 0.28). In conclusion, we think iceA should not be used as a reliable marker for predicting the clinical outcome of H. pylori infection.
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Affiliation(s)
- A A Ashour
- Laboratory of Molecular Biology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil, 30130-100
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Yahav J, Fradkin A, Weisselberg B, Diver-Haver A, Shmuely H, Jonas A. Relevance of CagA positivity to clinical course of Helicobacter pylori infection in children. J Clin Microbiol 2000; 38:3534-7. [PMID: 11015359 PMCID: PMC87432 DOI: 10.1128/jcm.38.10.3534-3537.2000] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
A potential virulence determinant of Helicobacter pylori is the cagA gene product. To determine the relevance of the expression of CagA to the clinical picture and outcome of H. pylori infection in children, we examined 104 consecutive children diagnosed with H. pylori infection. Serum samples were collected to test for the presence of immunoglobulin G (IgG) anti-CagA antibodies. Forty-five patients (43%) had antibodies to the CagA protein (group I), and 59 did not (group II). Seropositive patients had a longer prediagnostic history of abdominal pain (P = 0.02), more severe abdominal pain (defined as ulcer pain) (P = 0.05), a higher prevalence of duodenal ulcer (38 versus 7%; P<0.01), more active chronic gastritis (82 versus 32%; P<0.001), and a higher titer of serum IgG anti-H. pylori antibodies (P<0.001). Ninety percent of the patients were monitored for 27+/-18 months. On multivariate analysis, CagA-negative patients had a 3.8-fold-higher chance of achieving a disease-free state than CagA-positive patients (95% confidence interval, 1.5- to 9.5-fold). We conclude that infection with CagA-producing strains of H. pylori is a risk factor for severe clinical disease and ongoing infection.
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Affiliation(s)
- J Yahav
- Helicobacter Research Center, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel.
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Rocha GA, Oliveira AM, Queiroz DM, Carvalho AS, Nogueira AM. Immunoblot analysis of humoral immune response to Helicobacter pylori in children with and without duodenal ulcer. J Clin Microbiol 2000; 38:1777-81. [PMID: 10790098 PMCID: PMC86586 DOI: 10.1128/jcm.38.5.1777-1781.2000] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Several studies have demonstrated that enzyme-linked immunosorbent assay is not a sensitive and specific method to diagnose Helicobacter pylori infection in children, especially in the younger ones. Since serum immune response can also be determined by immunoblotting and it permits the detection of antibodies to virulence factors such as CagA and VacA, we evaluated the accuracy of a commercial immunoblotting test to diagnose H. pylori infection and to assess the humoral immune response to different H. pylori antigens in 122 children who underwent upper gastrointestinal endoscopy. The presence of H. pylori was determined in antral biopsy specimens by culture, preformed urease test, and histological analysis. H. pylori was identified by microbiological and histopathological methods in 66 children (including all of the 21 who had duodenal ulcer). Antibodies to H. pylori were detected in 63 infected children and in 8 noninfected ones. The sensitivity, specificity, and positive and negative predictive values of the immunoblotting test were 95.5, 85.7, 88.7, and 94.1%, respectively. The number of immunoreactive bands increased with age (P = 0.003), and the bands of 35 kDa (P = 0.013); 89 kDa, the VacA antigen (P = 0.001); and 116 kDa, the CagA antigen (P = 0.00004) were more frequently observed in older children. The frequency of the bands of 89 kDa (P = 0.001) and 116 kDa (P = 0.03) was higher in children with duodenal ulcer than in H. pylori-positive children without the disease. In conclusion, the immunoblotting test appears to be useful for the diagnosis of H. pylori infection in children, even in the younger ones.
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Affiliation(s)
- G A Rocha
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
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