Diagnosis of Helicobacter pylori infection

Helicobacter pylori ( H.   pylori ) infection can be diagnosed by invasive techniques requiring endoscopy and biopsy (histological examination, culture, polymerase chain reaction) and by noninvasive techniques (serology, urea breath test, urine or blood, detection of H. pylori antigen in stool specimen). At present, no single test can be absolutely relied upon to detect colonization by H. pylori , and a combination of two tests is recommended if feasible. The tests used should depend on the clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy, and the availability of the tests. Some clinical circumstances warrant invasive studies, principally patients with alarm symptoms (bleeding, weight loss, etc.) as well as older patients with new-onset dyspepsia. Endoscopy may also be advisable in patients who have failed eradication therapy and need culture and antimicrobial sensitivity testing to determine an appropriate regimen. Recent studies have also demonstrated that a strategy to `test and treat' for H. pylori in uninvestigated, young (< 50 years), dyspeptic patients in primary care is safe and reduces the need for endoscopy. Indeed, a number of clinical guidelines recommend noninvasive testing followed by treatment of H. pylori for dyspeptic patients in primary care based on clinical and economic analyses.     

Gastric MALT-lymphoma and Helicobacter pylori infection

The presence of lymphoid tissue in the gastric mucosa is virtually pathognomonic of Helicobacter pylori infection. This lymphoid tissue has mucosa–associated lymphoid tissue (MALT) characteristics suggesting that H. pylori infection may represent a stimulus for the growth of gastric MALT lymphoma. H. pylori can be detected in more than 90% of patients with low–grade gastric MALT lymphoma supporting the aetiological role of the organism. The strongest evidence for the significance of H. pylori in the pathogenesis of low aetological–grade gastric MALT lymphoma is provided by clinical studies showing that cure of H. pylori infection is followed by a complete regression of these tumours in most patients. This paper reviews the current knowledge about antibacterial treatment of low–grade gastric MALT lymphoma, and immunological and molecular aspects in the pathogenesis of the disease.     

Clarithromycin for Helicobacter pylori infection

Helicobacter pylori, a Gram-negative organism that survives in the deep mucus layer and attaches to the gastric surface cells, is estimated to be present in up to one-half of the US population. Chronic H. pylori infection causes chronic gastritis, peptic ulcer diseases and even gastric cancer. Cure of the infection leads to healing of gastric inflammation, prevention of development of peptic ulcer, as well as accelerated healing of peptic ulcers, and prevention of ulcer recurrence. Treatment of H. pylori has undergone substantial evolution over the past decade. Despite the in vitro susceptibility, results from single or even dual drug therapy is typically unsatisfactory and the best therapy is yet to be defined. The best current therapies for H. pylori infection consist of a proton pump inhibitor (PPI) or ranitidine bismuth citrate and two antibiotics (triple therapies), or bismuth, tetracycline, metronidazole and a PPI (quadruple therapy). Clarithromycin is one of the most useful antimicrobials against H. pylori. It is an acid-stable macrolide with a broad spectrum of antibacterial activity, well absorbed with a wide tissue distribution and with mild side effects. Clarithromycin has a low minimum inhibitory concentration (MIC₅₀) for H. pylori and its effect is potentiated by acid inhibition. When combined with a PPI or ranitidine bismuth citrate and amoxicillin or metronidazole, eradication rates of more than 95% can be achieved with susceptible organisms. However, the prevalence of primary and acquired clarithromycin resistance, which is due to mutations within a conserved loop of 23S rRNA of H. pylori, is increasing. In practice, the presence of clarithromycin resistance usually implies reduced success when clarithromycin-containing regimes are used. There is a need for improved therapies for H. pylori where antibiotic resistance is less of a problem.     

Clarithromycin for Helicobacter pylori infection

Helicobacter pylori, a Gram-negative organism that survives in the deep mucus layer and attaches to the gastric surface cells, is estimated to be present in up to one-half of the US population. Chronic H. pylori infection causes chronic gastritis, peptic ulcer diseases and even gastric cancer. Cure of the infection leads to healing of gastric inflammation, prevention of development of peptic ulcer, as well as accelerated healing of peptic ulcers, and prevention of ulcer recurrence. Treatment of H. pylori has undergone substantial evolution over the past decade. Despite the in vitro susceptibility, results from single or even dual drug therapy is typically unsatisfactory and the best therapy is yet to be defined. The best current therapies for H. pylori infection consist of a proton pump inhibitor (PPI) or ranitidine bismuth citrate and two antibiotics (triple therapies), or bismuth, tetracycline, metronidazole and a PPI (quadruple therapy). Clarithromycin is one of the most useful antimicrobials against H. pylori. It is an acid-stable macrolide with a broad spectrum of antibacterial activity, well absorbed with a wide tissue distribution and with mild side effects. Clarithromycin has a low minimum inhibitory concentration (MIC50) for H. pylori and its effect is potentiated by acid inhibition. When combined with a PPI or ranitidine bismuth citrate and amoxicillin or metronidazole, eradication rates of more than 95% can be achieved with susceptible organisms. However, the prevalence of primary and acquired clarithromycin resistance, which is due to mutations within a conserved loop of 23S rRNA of H. pylori, is increasing. In practice, the presence of clarithromycin resistance usually implies reduced success when clarithromycin-containing regimes are used. There is a need for improved therapies for H. pylori where antibiotic resistance is less of a problem.     

幽门螺杆菌粪便抗原用于幽门螺杆菌感染检验观察

目的分析幽门螺杆菌粪便抗原（HpSA）对幽门螺杆菌感染的诊断价值。方法收集304例患者粪便标本,运用ELISA法定性检测HpSA,同时对照用快速尿素酶试验、Gram染色镜检联合检测的胃黏膜标本。结果HpSA的敏感度为96．7％（240／249）,特异度为90．1％（44／49）,阳性预测值为96．4％（240／249）,阴性预测值为80．0％（44／55）,准确率为93．4％（284／304）。结论粪便HpSA检测具有操作简便、省时等特点,是较理想的非侵人性的Hp诊断方法。     

Rapid eradication of Helicobacter pylori infection

Background/aims: Current Helicobacter pylori eradication therapy for peptic ulcer disease usually involves a 2-week course of either a bismuth preparation or omeprazole in combination with antibiotics. We have studied a shorter, 7-day course of treatment to assess efficacy and tolerability. Methods: Four hundred and thirty-six patients, in three non-randomized groups, received omeprazole (40 mg mane), amoxycillin (500 mg t.d.s.) and metronidazole (400 mg t.d.s.): 308 patients received the triple combination for 14 days; 80 patients were treated for 7 days; and 48 patients received omeprazole and amoxycillin for 7 days but metronidazole for only 5 days. Results: Helicobacter pylori was eradicated in 89.5%, 91.1% and 87.5%, respectively (98.3%, 92.9% and 100% of metronidazole-sensitive isolates and 75.6% and 88.2% of metronidazole-resistant isolates in the first two groups). Side effects were significantly more frequent in patients who received 14 days (49%) compared with 7 days of treatment (33%); only 8/308 and 1/128 patients, respectively, failed to complete the course. Conclusions: On the basis of efficacy, tolerability and cost, we conclude that a 7-day course of the omeprazole (40 mg mane), amoxycillin (500 mg t.d.s.) plus metronidazole (400 mg t.d.s.) combination is effective therapy for the eradication of H. pylori.     

The treatment of Helicobacter pylori infection

Indications for eradication of Helicobacter pylori infection have widened since the National Institutes of Health consensus conference in 1994. It is argued that they should now include infected patients with non-ulcer dyspepsia, those concerned about the risk of gastric cancer, patients with gastric lymphoma, and those requiring long-term treatment with a proton pump inhibitor. Problems with existing clinical trials are discussed, and the results of different treatment regimens are discussed. It is proposed that future eradication trials should investigate H. pylori -infected subjects identified by serology, rather than ulcer patients, and that eradication is proved only by a pair of ¹³C-urea breath tests.     

Gastro-oesophageal reflux disease and Helicobacter pylori infection

Gastro-oesophageal reflux disease (GERD) and Helicobacter pylori infection are common conditions that frequently coexist. Controversy continues regarding the role of H. pylori infection in GERD. The results of some studies suggest that eradication of H. pylori may increase the risk for developing GERD, and some experts have suggested that chronic H. pylori infection may be of benefit. This article reviews the data on H. pylori infection and GERD and its treatment.     

Iron deficiency anaemia and Helicobacter pylori infection

Iron deficiency anaemia (IDA) is the most common form of anaemia world-wide. IDA is the simple result of an imbalance between iron loss and absorption. Gastric function with hydrochloric and ascorbic acid is essential for iron absorption. Some strains of Helicobacter pylori are able to acquire iron, competing with the host. A large percentage of patients with atrophic body gastritis (ABG) develop IDA and 61% of them are H. pylori positive. Recent evidence suggests that H. pylori infection could cause IDA in the absence of peptic ulcer or other upper gastrointestinal (GI) tract bleeding lesions. Gastritis extending to the corpus and a high bacterial load are features of these patients. About 70% of IDA patients with ABG or H. pylori gastritis are premenopausal women. Both ABG and H. pylori gastritis should be considered when evaluating the GI tract of patients with iron deficiency anaemia.     

Evolving therapy for Helicobacter pylori infection

Helicobacter pylori infection is a widespread disease causing significant morbidity and mortality, with relevant economic impact. A 7-day triple regimen (proton pump inhibitor together with two antibiotics) is currently suggested as first-line treatment, but the success rate following such a therapy is decreasing. Therefore, new drugs or novel therapeutic approaches are needed. Patents of new antibiotics have been claimed, such as both erythromycin and rifamycin derivatives, and new polycyclic compounds, showing a very powerful antibacterial activity in vitro. Patents of either H. pylori urease inhibitors or new proton pump inhibitors are also of great interest. Several attempts have been made to create vaccines for H. pylori infection, with interesting results in animal models. Experimentation in humans is ongoing.     

Outcomes research in Helicobacter pylori infection

While the medical community has accepted the role of H. pylori in the pathogenesis of peptic ulcer disease, confusion persists among clinicians regarding when and on which patients to attempt H. pylori eradication. Thus, the objective for outcomes research in H. pylori is to help clinicians identify which patients benefit from H. pylori eradication and to determine the cost-effective strategies for their diagnosis, treatment and follow-up care.
Economic evaluation of the impact of H. pylori infection has focused primarily on assessment of patient with documented peptic ulcer disease, with particular attention to costs of pharmaceuticals. However, drug costs are only one portion of the total costs of management for patients with acid-related disorders and therefore must be put in the appropriate context. Additional aspects of patient benefit (e.g. patient satisfaction) and health-care expenditures (e.g. over-the-counter medications, specialist visits, hospitalizations) must be included in an evaluation of the value of a particular diagnostic test, treatment, clinical guideline or disease management strategy.
As a result of the high quality and quantity of data emerging, it can be safely said that H. pylori eradication is cost-effective in selected patient populations: newly documented peptic ulcer disease; history of peptic ulcer disease and taking maintenance therapy; and suspected peptic ulcer disease using a serological test to guide initial treatment. The role of eradication in other areas, for example, patients with non-ulcer dyspepsia and screening to prevent gastric cancer, remains to be seen. In addition to the performance of rigorous studies, researchers must respond to the 'information overload' on busy clinicians, by effectively disseminating their findings. If data generated from outcomes research are not integrated into everyday clinical practice, the enormous benefits associated with H. pylori eradication will not be achieved.     

Novel therapies for Helicobacter pylori infection

Background:

Increasing antibiotic resistance has begun to impair our ability to cure Helicobacter pylori infection.

Aim:

To evaluate orally administered novel therapies for the treatment of H. pylori infection.

Methods:

Healthy H. pylori infected volunteers received: (a) hyperimmune bovine colostral immune globulins, (b) an oligosaccharide containing an H. pylori adhesion target, Neu5Aca2-3Galb1–4Glc-(3′-sialyllactose), or (c) recombinant human lactoferrin. Outcome was assessed by urea breath test or histological assessment of the number of H. pylori present.

Results:

None of the novel therapies appeared effective and no adverse events occurred.

Conclusion:

Although in vitro data appeared promising, in vivo results were disappointing. Higher doses, longer duration of therapy, adjunctive acid suppression, or a combination could possibly yield better results.

     

Clarithromycin-amoxycillin therapy for Helicobacter pylori infection

Background: More convenient therapies are needed to treat Helicobacter pylori infection successfully. Clarithromycin and amoxycillin are effective against H. pylori both in vivo and in vitro. Recent success with a high dose amoxycillin-metronidazole combination therapy led us to evaluate clarithromycin-amoxycillin dual therapy for H. pylori infection. Methods: We tested the combination of clarithromycin 500 mg t.d.s. with meals plus amoxycillin 750 mg t.d.s. with meals for 10 days for its effect on H. pylori infection in 29 patients with documented H. pylori peptic ulcers. There were 27 men and 2 women, ranging in age from 23 to 77 years. H. pylori and ulcer status were evaluated at entry and at least 4 weeks after ending antimicrobial therapy. For ulcer healing, ranitidine 300 mg was given each evening for 6 weeks. H. pylori status was determined by CLOtest and histology. Results: H. pylori infection was cured in 86% (95% CI = 78–99%). Compliance averaged 93% by pill count. Ten patients (34%) experienced mild side effects: eight reported dysgeusia and two had mild diarrhoea; none discontinued therapy because of side effects. Conclusion: We conclude that dual therapy with clarithromycin and amoxycillin is a safe and effective alternative regimen for the successful treatment of H. pylori infections.     

Natural history and epidemiology of Helicobacter pylori infection

Helicobacter pylori is a common bacterium infecting about half the world's population. It is causally linked with a diverse spectrum of gastrointestinal clinical disorders including peptic ulcer disease, gastric cancer, and gastric MALT lymphoma. The principal reservoir is the human stomach, and transmission probably occurs by person-to-person passage. Prevalence rates are generally much higher in developing countries compared to developed countries, although there are subgroups within many regions with higher H. pylori prevalence than in the general population. The prevalence of H. pylori varies by geographical location, ethnic background, socioeconomic conditions, and age. Recent studies suggest decreasing prevalence in developed countries or those with rapidly improving socioeconomic conditions. Comparative studies of the two fully sequenced H. pylori genomes are providing understanding of its large genetic diversity and bacterial virulence factors. The discovery of the type IV secretion system in H. pylori and its role in translocation of the CagA protein from the bacterial cell into the host epithelial cell provides insight into how host–bacterial interaction may lead to host disease. Cytokine promoter polymorphisms are determinants important in host gastric acid secretion status. Understanding the changing trends in H. pylori epidemiology, details of its transmission pathways, and the bacterial and host determinants leading to gastroduodenal disease remain the challenges in this area. Global epidemiological studies, advances in technology, and medical interventions have converged to help clarify the mechanisms of interaction between this ubiquitous micro-organism and its host that result in its diverse clinical manifestations.     

The cost of diagnosing Helicobacter pylori infection

Non-invasive testing and treatment for Helicobacter pylori has been recommended for dyspeptic patients in primary care and a number of recent studies have demonstrated the cost-effectiveness of this approach. As the prevalence of H. pylori infection declines, the positive and negative predictive values of individual tests will change. Cost-effectiveness is important in determining the appropriate test in individual populations. Recent studies have shown that the stool antigen test and the urea breath test have high sensitivity and specificity in the detection of H. pylori infection before and after therapy.
Cost-effectiveness studies have shown that when the prevalence of H. pylori infection is low or intermediate, serological tests have relatively poor accuracy compared with the stool test or the urea breath test. In populations with low or intermediate prevalence (<60%) these tests should be preferred to ELISA serology or office-based whole-blood test or serology. This is particularly true when the prevalence of H. pylori infection is less than 30% as is seen in many developed countries. When the prevalence of H. pylori infection is high (>60%), low-cost antibody tests are cost-effective.     

Treatment of Helicobacter pylori infection in children

The majority of Helicobacter pylori (H. pylori) infections appear to be acquired during childhood. Despite this fact, the natural history of H. pylori infection in children, such as the mode of acquisition, the clinical symptoms and signs of infection and the appropriate treatment, is poorly understood. There is no consensus regarding which children with H. pylori infection deserve treatment nor is there agreement on the appropriate treatment regimen. This stems from the lack of controlled studies into H. pylori infection during childhood. For example, there have been no controlled studies to determine effective treatment of H. pylori infection in children. Although published guidelines for the treatment of childhood H. pylori infection do not currently exist, there is reasonable evidence to support treatment in children with gastric or duodenal ulcer, gastric MALT (mucosa-associated lymphoid tissue) lymphoma and atrophic gastritis. There is no strong evidence to recommend treatment of children with H. pylori infection and recurrent abdominal pain, asymptomatic infection, children in chronic care facilities and children who have a family member with H. pylori infection. Current evidence suggests that single and dual therapy regimens for H. pylori infection in children are not effective. Triple therapy , generally the combination of 2 antibiotics and a proton pump inhibitor, given two times daily for 2 weeks appears to offer the best current treatment.     

Antral gastrin cell hyperfunction and Helicobacter pylori infection

Background : Antral gastrin cell hyperfunction (AGCH), is a rare cause of duodenal ulcer associated with non-tumour hypergastrinaemia and acid hypersecretion.
Aim : To investigate the role of Helicobacter pylori in AGCH.
Patients : Twelve AGCH patients and eight H. pylori -positive non-hypergastrinaemic duodenal ulcer patients were compared.
Methods : Basal and peak acid outputs, gastrin-stimulation (meal and bombesin) tests, and immunohistochemistry for antral G and D cells were performed. One year after H. pylori eradication, six AGCH patients were again investigated with the same tests.
Results : Significantly more basal, and stimulated gastrin and acid secretion, were found in AGCH compared to the H. pylori -positive duodenal ulcer patients ( P <0.01). G cell counts were significantly higher in AGCH than in duodenal ulcer patients (118.8, range 58–192.4, vs. 86.1, range 49–184; P <0.05), and the resulting G/D cell ratio was also higher in AGCH patients (4.2, range 2.6–5.6, vs. 3.3, range 1.9–4.3; P <0.05). H. pylori was present in the gastric mucosa of all 12 AGCH patients. Cure of infection in six AGCH individuals resulted in marked a decrease of gastrin levels associated with a significant (23.7%; P <0.05) decrease of G cell count and an increase (12%; P <0.05) of D cell count.
Conclusions : The results indicate that AGCH may result from H. pylori overstimulation of gastrin cell function in patients with some presently undefined, familial predisposition and that an imbalance of the G/D cell ratio may have a role in the genesis of hypergastrinaemia.