The effect of CagA status on response to Helicobacter pylori eradication therapy in Western Turkey

If cytotoxin-associated gene A (CagA) status affects the response rates of therapy, then it may be possible to predict Helicobacter pylori eradication rates. We aimed to evaluate the response to eradication treatment of H. pylori infection in CagA-positive and CagA-negative patients. A total of 184 patients (93 males, 91 females, mean age 42.6 ± 12.8 years) with H. pylori-positive chronic gastritis were studied. Subjects underwent a gastroscopy and biopsy specimens were taken from the gastric antrum, body, and fundus. Before the eradication therapy was given all patients were tested for CagA, TNF-alpha and gastrin levels. They were then prescribed lansoprazole (30 mg bid), clarithromycin (500 mg bid), and amoxicillin (1.0 mg bid) for one week. On the 8th week a second endoscopy was performed and further biopsy specimens were obtained from the same sites as in the initial endoscopy. One hundred and twenty-seven patients (69.1%) were found to be CagA positive and 57 patients (30.9%) were CagA negative. The total eradication rate was 82.6%. In the CagA-positive group this rate was 87.4%, and in the CagA-negative group it was 71.9% (P = 0.019). TNF-alpha levels were higher in the CagA-positive than in the CagA-negative group (P = 0.001). However, gastrin levels were not different between groups (P = 0.421). Our findings revealed that CagA-negative status might be a risk factor for failure of H. pylori triple therapies. The CagA pathogenicity island gives a growth advantage to H. pylori strains and has been associated with an increase in the inflammatory response at the gastric mucosal level. These properties could make CagA-positive H. pylori strains more susceptible to antibiotics.

Secondary analysis of effectivness of tinidazole-containing-quadruple eradication therapy in asymptomatic H. pylori infected children in El Paso

Helicobacter pylori infection is frequently acquired during childhood. This microorganism is known to cause gastritis, and duodenal ulcer in pediatric patients, however most children remain completely asymptomatic to the infection. Currently there is no consensus in favor of treatment of H. pylori infection in asymptomatic children. The firstline of treatment for this population is triple medication therapy including two antibacterial agents and one proton pump inhibitor for a 2 week duration course. Decreased eradication rate of less than 75% has been documented with the use of this first-line therapy but novel tinidazole-containing quadruple sequential therapies seem worth investigating. None of the previous studies on such therapy has been done in the United States of America. As part of an iron deficiency anemia study in asymptomatic H. pylori infected children of El Paso, Texas, we conducted a secondary data analysis of study data collected in this trial to assess the effectiveness of this tinidazole-containing sequential quadruple therapy compared to placebo on clearing the infection. Subjects were selected from a group of asymptomatic children identified through household visits to 11,365 randomly selected dwelling units. After obtaining parental consent and child assent a total of 1,821 children 3-10 years of age were screened and 235 were positive to a novel urine immunoglobulin class G antibodies test for H. pylori infection and confirmed as infected using a 13C urea breath test, using a hydrolysis urea rate >10 μg/min as cut-off value. Out of those, 119 study subjects had a complete physical exam and baseline blood work and were randomly allocated to four groups, two of which received active H. pylori eradication medication alone or in combination with iron, while the other two received iron only or placebo only. Follow up visits to their houses were done to assess compliance and occurrence of adverse events and at 45+ days post-treatment, a second urea breath test was performed to assess their infection status. The effectiveness was primarily assessed on intent to treat basis (i.e., according to their treatment allocation), and the proportion of those who cleared their infection using a cut-off value >10 μg/min of for urea hydrolysis rate, was the primary outcome. Also we conducted analysis on a per-protocol basis and according to the cytotoxin associated gene A product of the H. pylori infection status. Also we compared the rate of adverse events across the two arms. On intent-to-treat and per-protocol analyses, 44.3% and 52.9%, respectively, of the children receiving the novel quadruple sequential eradication cleared their infection compared to 12.2% and 15.4% in the arms receiving iron or placebo only, respectively. Such differences were statistically significant (p<0.001). The study medications were well accepted and safe. In conclusion, we found in this study population, of mostly asymptomatically H. pylori infected children, living in the US along the border with Mexico, that the quadruple sequential eradication therapy cleared the infection in only half of the children receiving this treatment. Research is needed to assess the antimicrobial susceptibility of the strains of H. pylori infecting this population to formulate more effective therapies. ^

Efficacy of a 7-day course of furazolidone, levofloxacin, and lansoprazole after failed Helicobacter pylori eradication

Background: Increasing resistance to clarithromycin and nitroimidazole is the main cause of failure in the Helicobacter pylori eradication. The ideal retreatment regimen remains unclear, especially in developing countries, where the infection presents high prevalence and resistance to antibiotics. The study aimed at determining the efficacy, compliance and adverse effects of a regimen that included furazolidone, levofloxacin and lansoprazole in patients with persistent Helicobacter pylori infection, who had failed to respond to at least one prior eradication treatment regimen. Methods: This study included 48 patients with peptic ulcer disease. Helicobacter pylori infection was confirmed by a rapid urease test and histological examination of samples obtained from the antrum and corpus during endoscopy. The eradication therapy consisted of a 7-day twice daily oral administration of lansoprazole 30 mg, furazolidone 200 mg and levofloxacin 250 mg. Therapeutic success was confirmed by a negative rapid urease test, histological examination and 14C- urea breath test, performed 12 weeks after treatment completion. The Chi-square method was used for comparisons among eradication rates, previous treatments and previous furazolidone use. Results: Only one of the 48 patients failed to take all medications, which was due to adverse effects (vomiting). Per-protocol and intention-to-treat eradication rates were 89% (95% CI-89%-99%) and 88% (88-92%), respectively. Mild and moderate adverse effects were reported by 41 patients (85%). For patients with one previous treatment failure, the eradication rate was 100%. Compared to furazolidone-nave patients, eradication rates were lower in those who had failed prior furazolidone-containing regimen(s) (74% vs. 100%, p = 0.002). Conclusion: An empiric salvage-regimen including levofloxacin, furazolidone and lansoprazole is very effective in the eradication of Helicobacter pylori, particularly in patients that have failed one prior eradication therapy.

Effect of helicobacter pylori eradication on TLR2 and TLR4 expression in patients with Gastric Lesions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of Helicobacter pylori eradication among adults with intellectual disability

Background Compared to the general population, Helicobacter pylori infection is more common among adults with intellectual disability (ID) and is associated with greater levels of disability, maladaptive behaviour, and institutionalization. Little information exists about the effects of eradication therapy in this group, so we aimed to evaluate: (1) success of a standard H. pylori eradication protocol; (2) frequency of side-effects; and (3) impact of eradication on level of functional ability and maladaptive behaviour. Method A cohort of adults with ID underwent assessment of their levels of function and maladaptive behaviour, medical history, physical examination, and H. pylori testing using serology and faecal antigen tests. Some received standard H. pylori eradication therapy. Twelve months later, participants underwent repeat assessment, were grouped by change in H. pylori status and compared. Results Of 168 participants, 117 (70%) were currently infected with H. pylori at baseline, and 96 (82%) of the 117 were given standard H. pylori eradication therapy. The overall eradication rate was 61% but 31% reported side-effects. Institutional status of the participants, their level of behaviour or function, and number of comorbid medical conditions were not associated with failure of eradication. There were no statistically significant differences in level of behaviour or function, ferritin, or weight between the groups in whom H. pylori was eradicated or stayed positive. Conclusion Adults with ID have lower H. pylori eradication and higher side-effect rates than the general population. Levels of maladaptive behaviour and disability did not improve with eradication and thus greater levels of maladaptive behaviour or disability appear to be risk factors for, rather than consequences of, H. pylori infection.

Australian doctors' beliefs and practice regarding Helicobacter pylori

Objective: To determine beliefs and behaviours of Australian doctors regarding Helicobacter pylori. Design: Anonymous reply-paid postal survey mailed in December 1995 and again in March 1996. Subjects: All members on the mailing lists of the Gastroenterological Society of Australia Endoscopy Section (n = 397) and the Australian Society of Infectious Diseases (n = 264; those without medical qualifications were asked not to reply), and 400 general practitioners (GPs) randomly selected from the Royal Australian College of General Practitioners. Main outcome measures: Differences between specialist groups in belief in a causative association between H. pylori and peptic disease and in use of eradication therapy and pre- and post-treatment testing for H. pylori. Results: 92.6% of doctors believed H. pylori causes duodenal ulcer, with GPs significantly less likely to believe than gastroenterologists (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.00-0.81). In duodenal ulcer, 93.4% of doctors believed H. pylori eradication therapy should be given, but fewer (83.4%) claimed to give it always or mostly, with GPs less likely to report giving it than gastroenterologists (OR, 0.06; 95% CI, 0.02-0.19). For non-ulcer dyspepsia, gastrointestinal surgeons were more likely than gastroenterologists to believe in a causative link with H. pylori (OR, 5.6; 95% CI, 3.0-10.7) and in a need for eradication therapy (OR, 3.6; 95% CI, 1.7-7.7). Most doctors (79.3%) believed in confirming the presence of H. pylori before eradication therapy in duodenal ulcer. Only 51.6% believed post-eradication testing necessary (45.5%), yet 79.1% reported performing it. Conclusions: Significant differences exist between specialist groups in beliefs and self-reported behaviours regarding H. pylori.

Helicobacter pylori Reinfection in Brazilian Patients with Peptic Ulcer Disease: A 5-Year Follow-Up

Background: The Helicobacter pylori reinfection seems to be higher in developing countries, than in developed ones. The aim of the study was to determine the annual recurrence rate of H. pylori, in Brazilian patients with peptic ulcer disease, in a 5-year follow-up. Methods: Patients, with peptic ulcer disease diagnosed by upper digestive endoscopy (UDE) and H. pylori infection verified by histological analysis, rapid urease test, polymerase chain reaction, and urea breath test (UBT), were treated for bacterial eradication. The cure of the infection was verified using the same tests, 3 months after. Clinical evaluation and UBT were performed after sixth and ninth month. After 1 year of follow-up, UBT and UDE were repeated. Up to the fifth year, patients were assessed twice a year and an UBT was performed annually. The patients included and all the reinfected were tested for 15 different genes of the H. pylori. Results: One hundred and forty-seven patients were followed: 19 for 1 year, eight for 2 years, four for 3 years, five for 4 years, and 98 for 5 years, totaling 557 patients/years. Recurrence did not occur in the first year. In the second year, two patients were reinfected; in the third, four patients; in the fourth, three patients; and in the fifth, one patient. The total of reinfected patients was 10. The annual reinfection rate was 1.8%. Conclusion: Brazil presents a low prevalence of H. pylori reinfection, similar to the developed countries.

Oral cavity is not a reservoir for Helicobacter pylori in infected patients with functional dyspepsia

Helicobacter pylori infection is very prevalent in Brazil, infecting almost 65% of the population. The aim of this study was to evaluate the presence of this bacterium in the oral cavity of patients with functional dyspepsia (epigastric pain syndrome), establish the main sites of infection in the mouth, and assess the frequency of cagA and vacA genotypes of oral H. pylori. All 43 outpatients with epigastric pain syndrome, who entered the study, were submitted to upper gastrointestinal endoscopy to rule out organic diseases. Helicobacter pylori infection in the stomach was confirmed by a rapid urease test and urea breath tests. Samples of saliva, the tongue dorsum and supragingival dental plaque were collected from the oral cavity of each subject and subgingival dental plaque samples were collected from the patients with periodontitis; H. pylori infection was verified by polymerase chain reaction using primers that amplify the DNA sequence of a species-specific antigen present in all H. pylori strains; primers that amplify a region of urease gene, and primers for cagA and vacA (m1, m2, s1a, s1b, s2) genotyping. Thirty patients harbored H. pylori in the stomach, but it was not possible to detect H. pylori in any oral samples using P1/P2 and Urease A/B. The genotype cagA was also negative in all samples and vacA genotype could not be characterized (s-m-). The oral cavity may not be a reservoir for H. pylori in patients with epigastric pain syndrome, the bacterium being detected exclusively in the stomach.

Molecular fingerprint of human gastric cell line infected by Helicobacter pylori

Helicobacter pylori infection represents a serious health problem, given its association with serious gastric diseases as gastric ulcers, cancer and MALT lymphoma. Currently no vaccine exists and antibiotic-based eradication therapy is already failing in more than 20% of cases. To increase the knowledge on the infection process diverse gastric cell lines, e.g. the adenocarcinona gastric (AGS) cell line, are routinely used has in vitro models of gastric epithelia. In the present work the molecular fingerprint of infected and non-infected AGS cell lines, by diverse H. pylori strains, was acquired using vibrational infrared spectroscopy. These molecular fingerprints enabled to discriminate infected from non-infected AGS cells, and infection due to different strains, by performing Principal Component Analysis. It was also possible to estimate, from the AGS cells molecular fingerprint, the effect of the infection on diverse biochemical and metabolic cellular status. In resume infra-red spectroscopy enabled the acquisition of infected AGS cells molecular fingerprint with minimal sample preparation, in a rapid, high-throughput, economic process yielding highly sensitive and informative data, most useful for promoting critical knowledge on the H. pylori infection process. © 2015 IEEE.

RESISTANCE TO AMOXICILLIN, CLARITHROMYCIN AND CIPROFLOXACIN OF Helicobacter pylori ISOLATED FROM SOUTHERN BRAZIL PATIENTS

Introduction: Helicobacter pylori is a bacteria which infects half the world population and is an important cause of gastric cancer. The eradication therapy is not always effective because resistance to antimicrobials may occur. The aim of this study was to determine the susceptibility profile of H. pylori to amoxicillin, clarithromycin and ciprofloxacin in the population of Southern Brazil. Material and methods: Fifty four samples of H. pylori were evaluated. The antibiotics susceptibility was determined according to the guidelines of the British Society for Antimicrobial Chemotherapy and the Comité de l'Antibiogramme de la Société Française de Microbiologie. Results: Six (11.1%) H. pylori isolates were resistant to clarithromycin, one (1.9%) to amoxicillin and three (5.5%) to ciprofloxacin. These indices of resistance are considered satisfactory and show that all of these antibiotics can be used in the empirical therapy. Conclusion: The antibiotics amoxicillin and clarithromycin are still a good option for first line anti-H. pylori treatment in the population of Southern Brazil.

Expressão gênica e proteica e cinética celular no processo inflamatório induzido pela Helicobacter pylori antese após terapia de erradicação

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeito do tratamento da H. pylori na expressão de citocinas e microRNAs associados ao processo inflamatório

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeito da infecção e da terapia de erradicação da Helicobacter pylori na expressão gênica de paciente com gastrite crônica

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Medizinischer und gesundheitsökonomischer Nutzen der Untersuchung auf Helicobacter pylori-Besiedlung mittels 13C-Harnstoff-Atemtest in der Primärdiagnostik im Vergleich zu invasiven und nichtinvasiven diagnostischen Verfahren

Hintergrund: Helicobacter pylori (H. pylori) zählt trotz abnehmender Inzidenz zu den häufigsten bakteriellen Infektionskrankheiten des Menschen. Die Infektion mit H. pylori ist ein Risikofaktor für Krankheiten wie gastroduodenale Geschwüre, Magenkarzinomen und MALT (Mucosa Associated Lymphoid Tissue)-Lymphomen. Zur Diagnostik von H. pylori stehen verschiedene invasive und nichtinvasive Verfahren zur Verfügung. Der 13C-Harnstoff-Atemtest wird zur Kontrolle einer Eradikationstherapie empfohlen, kommt in der Primärdiagnostik von H. pylori derzeit jedoch nicht standardmäßig in Deutschland zum Einsatz. Fragestellung: Welchen medizinischen und gesundheitsökonomischen Nutzen hat die Untersuchung auf H. pylori-Besiedlung mittels 13C-Harnstoff-Atemtest in der Primärdiagnostik im Vergleich zu invasiven und nichtinvasiven diagnostischen Verfahren? Methodik: Basierend auf einer systematischen Literaturrecherche in Verbindung mit einer Handsuche werden Studien zur Testgüte und Kosten-Effektivität des 13C-Harnstoff-Atemtests im Vergleich zu anderen diagnostischen Verfahren zum primären Nachweis von H. pylori identifiziert. Es werden nur medizinische Studien eingeschlossen, die den 13C-Harnstoff-Atemtest direkt mit anderen H. pylori-Testverfahren vergleichen. Goldstandard ist eines oder eine Kombination der biopsiebasierten Testverfahren. Für die gesundheitsökonomische Beurteilung werden nur vollständige gesundheitsökonomische Evaluationsstudien einbezogen, bei denen die Kosten-Effektivität des 13C Harnstoff-Atemtests direkt mit anderen H. pylori-Testverfahren verglichen wird. Ergebnisse: Es werden 30 medizinische Studien für den vorliegenden Bericht eingeschlossen. Im Vergleich zum Immunglobulin G (IgG)-Test ist die Sensitivität des 13C-Harnstoff-Atemtests zwölfmal höher, sechsmal niedriger und einmal gleich, und die Spezifität 13-mal höher, dreimal niedriger und zweimal gleich. Im Vergleich zum Stuhl-Antigen-Test ist die Sensitivität des 13C-Harnstoff-Atemtests neunmal höher, dreimal niedriger und einmal gleich, und die Spezifität neunmal höher, zweimal niedriger und zweimal gleich. Im Vergleich zum Urease-Schnelltest sind die Sensitivität des 13C-Harnstoff-Atemtests viermal höher, dreimal niedriger und viermal gleich und die Spezifität fünfmal höher, fünfmal niedriger und einmal gleich. Im Vergleich mit der Histologie ist die Sensitivität des 13C-Harnstoff-Atemtests einmal höher und zweimal niedriger und die Spezifität zweimal höher und einmal niedriger. In je einem Vergleich zeigt sich kein Unterschied zwischen 13C-Harnstoff-Atemtest und 14C-Harnstoff-Atemtest, sowie eine niedrigere Sensitivität und höhere Spezifität im Vergleich zur Polymerase-Kettenreaktion (PCR). Inwieweit die beschriebenen Unterschiede statistisch signifikant sind, wird in sechs der 30 Studien angegeben. Es werden neun gesundheitsökonomische Evaluationen in dem vorliegenden Bericht berücksichtigt. Die Test-and-Treat-Strategie mittels 13C-Harnstoff-Atemtest wird in sechs Studien mit einem Test-and-Treat-Verfahren auf Basis der Serologie sowie in drei Studien mit einem Test-and-Treat-Verfahren auf Basis des Stuhl-Antigen-Tests verglichen. Dabei ist das Atemtestverfahren dreimal kosteneffektiv gegenüber der serologischen Methode und wird von der Stuhl-Antigen-Test-Strategie einmal dominiert. Vier Studien beinhalten einen Vergleich der Test-and -Treat-Strategie auf Basis des 13C-Harnstoff-Atemtests mit einer empirischen antisekretorischen Therapie, wobei sich das Atemtesverfahren zweimal als kosteneffektive Prozedur erweist und zwei Studien einen Vergleich mit einer empirischen Eradikationstherapie. In fünf Studien wird das Test-and-Treat-Verfahren mittels 13C-Harnstoff-Atemtest einer endoskopiebasierten Strategie gegenübergestellt. Zweimal dominiert die Atemteststrategie die endoskopische Prozedur und einmal wird sie von dieser Strategie dominiert. Diskussion:Sowohl die medizinischen als auch die ökonomischen Studien weisen mehr oder minder gravierende Mängel auf und liefern heterogene Ergebnisse. So werden in der Mehrzahl der medizinischen Studien keine Angaben zur statistischen Signifikanz der berichteten Unterschiede zwischen den jeweiligen Testverfahren gemacht. Im direkten Vergleich weist der 13C-Harnstoff-Atemtest überwiegend eine höhere Testgüte als der IgG und der Stuhl-Antigen-Test auf. Aus den Vergleichen mit dem Urease-Schnelltest lassen sich keine Tendenzen bezüglich der Sensitivität ableiten, wohingegen die Spezifität des 13C-Harnstoff-Atemtests höher einzuschätzen ist. Für die Vergleiche des 13C-Harnstoff-Atemtest mit der Histologie, dem 14C-Harnstoff-Atemtest und der PCR liegen zu wenige Ergebnisse vor. In der eingeschlossenen ökonomischen Literatur deuten einige Studienergebnisse auf eine Kosten-Effektivität der Test-and-Treat-Strategie mittels 13C-Harnstoff-Atemtest gegenüber dem Test-and-Treat-Verfahren auf Basis der Serologie und der empirischen antiskretorischen Therapie hin. Um Tendenzen bezüglich der Kosten-Effektivität der Atemteststrategie gegenüber der Test-and-Treat-Strategie mittels Stuhl-Antigen-Test sowie der empirischen Eradikationstherapie abzuleiten, mangelt es an validen Ergebnissen bzw. ökonomischer Evidenz. Die Untersuchungsresultate hinsichtlich eines Vergleichs mit endoskopiebasierten Verfahren fallen diesbezüglich zu heterogen aus. Insgesamt kann keines der ökonomischen Modelle der Komplexität des Managements von Patienten mit dyspeptischen Beschwerden gänzlich gerecht werden. Schlussfolgerungen/Empfehlungen: Zusammenfassend ist festzuhalten, dass die Studienlage zur medizinischen und ökonomischen Beurteilung des 13C-Harnstoff-Atemtests im Vergleich zu anderen diagnostischen Methoden nicht ausreichend ist, um den Atemtest als primärdiagnostisches Standardverfahren im Rahmen einer Test-and-Treat-Strategie beim Management von Patienten mit dyspeptischen Beschwerden für die deutsche Versorgungslandschaft insbesondere vor dem Hintergrund der Leitlinien der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DGVS) anstelle einer endoskopiebasierten Methode zu empfehlen.

Short-term triple therapy with azithromycin for Helicobacter pylori eradication: Low cost, high compliance, but low efficacy

Background: The Brazilian consensus recommends a short-term treatment course with clarithromycin, amoxicillin and proton-pump inhibitor for the eradication of Helicobacter pylori ( H. pylori). This treatment course has good efficacy, but cannot be afforded by a large part of the population. Azithromycin, amoxicillin and omeprazole are subsidized, for several aims, by the Brazilian federal government. Therefore, a short-term treatment course that uses these drugs is a low-cost one, but its efficacy regarding the bacterium eradication is yet to be demonstrated. The study's purpose was to verify the efficacy of H. pylori eradication in infected patients who presented peptic ulcer disease, using the association of azithromycin, amoxicillin and omeprazole. Methods: Sixty patients with peptic ulcer diagnosed by upper digestive endoscopy and H. pylori infection documented by rapid urease test, histological analysis and urea breath test were treated for six days with a combination of azithromycin 500 mg and omeprazole 20 mg, in a single daily dose, associated with amoxicillin 500 mg 3 times a day. The eradication control was carried out 12 weeks after the treatment by means of the same diagnostic tests. The eradication rates were calculated with 95% confidence interval. Results: The eradication rate was 38% per intention to treat and 41% per protocol. Few adverse effects were observed and treatment compliance was high. Conclusion: Despite its low cost and high compliance, the low eradication rate does not allow the recommendation of the triple therapy with azithromycin as an adequate treatment for H. pylori infection.