Limited impact on endoscopy demand from a primary care based ‘test and treat’ dyspepsia management strategy: the results of a randomised controlled trial

BACKGROUND: Helicobacter pylori testing has been suggested as an alternative to endoscopy for young patients with dyspepsia. Secondary care studies have suggested that demand for endoscopy among this group could be reduced by up to 74%. However, the effect of H. pylori testing in the primary care setting, where the majority of dyspepsia is managed, is unclear. AIM: To determine the effects of providing a H. pylori serology service for GPs upon demand for open access endoscopy. DESIGN OF STUDY: A prospective randomised controlled trial. SETTING: Forty-seven general practices in Gloucestershire. METHOD: General practices were stratified by endoscopy referral rate and randomised into two groups. The intervention group was provided with access to H. pylori serology testing and encouraged to use it in place of endoscopy for patients aged under 55 years with dyspepsia. Endpoints were referral for endoscopy and serology use. RESULTS: There was a significant reduction in referrals for endoscopy in the intervention group compared to the control group: 18.8% (95% confidence interval = 5.0 to 30.6%; P = 0.009). CONCLUSIONS: Providing GPs with H. pylori serology testing reduced demand for open access endoscopy, but by less than previous studies had predicted.     

Role of Helicobacter pylori in gastrointestinal disease: implications for primary care of a revolution in management of dyspepsia.

The majority of patients with dyspepsia are managed in general practice. However, most of the literature on Helicobacter pylori and its association with gastrointestinal disease has originated from secondary care. This review summarizes the role of H pylori in dyspepsia from the perspective of primary care and suggests a new strategy for the management of dyspeptic patients in this setting. Recent meta-analyses and consensus statements have supported the use of eradication therapy as first-line treatment of peptic ulceration. Studies from primary care have supported the use of eradication therapy in patients who have H pylori related peptic ulcer disease and require long-term H2-antagonist medication, on both clinical benefit and cost-effectiveness grounds. Of the many regimens proposed for the eradication of H pylori, the best evidence supports a triple combination of bismuth, metronidazole and tetracycline. Regimens using proton pump inhibitors may be more acceptable to patients but lack good evidence from trials. Use of a positive serum enzyme-linked immunoabsorbent assay for H pylori antibodies as a criterion for endoscopic investigation has been shown to result in a 23% reduction in endoscopic workload. Further research should answer questions of importance to general practitioners, such as the role of eradication therapy in patients with nonulcer dyspepsia and the effectiveness of eradication of H pylori in the prevention of gastric cancer.     

Long-term follow up of patients with gastritis associated with Helicobacter pylori infection.

The aim of this study was to evaluate the long-term prognosis for patients suffering from gastritis associated with Helicobacter pylori infection, and in particular the proportion of cases progressing to peptic ulcer. The study was carried out in one urban general practice. One hundred and three patients who had presented with dyspepsia over the 1973-80 period and who were found to have a macroscopically normal endoscopy were reassessed between seven and 14 years later. Gastric antral biopsies had been taken routinely at endoscopy and were subsequently re-examined for the presence of H pylori. The patients' medical records were examined to establish their consulting rates over the follow-up period and whether they suffered from any other medical conditions. Patients were interviewed to assess the course of their dyspeptic symptoms. Comparison of patients who were unequivocally H pylori positive with those who were negative revealed no significant differences in the consultation rate for gastroenterological symptoms, in the proportion of patients referred to a hospital consultant or for further gastroenterological investigations or in the proportion reporting that their symptoms had improved. However, a statistically highly significant relationship was found between H pylori infection and hypertension. The results of this study have shown that there is a good prognosis for non-ulcer dyspepsia whether or not H pylori infection is present. The association between H pylori gastritis and hypertension clearly merits further investigation.     

Prevalence of Helicobacter pylori vacuolating cytotoxin and its allelic mosaicism as a predictive marker for Iranian dyspeptic patients

Helicobacter pylori infects the majority of the population in the developing countries. However, the rate of gastrointestinal complications such as peptic ulcers and gastric malignancies has no parallel with the infection. In order to determine whether cytotoxin (vacA) and its allelic polymorphism can serve as screening markers for such a population, H. pylori strains were isolated from one hundred and thirty two dyspeptic patients. H. pylori genomic DNA was extracted and underwent PCR-amplification for the cytotoxin alleles. Genotyping of the signal sequence region of the vacA gene identified 68% (70 out of 103) of patients with non ulcer dyspepsia (NUD) and 79% (23 out of 29) of the patients with peptic ulcer disease (PUD) possessing the s1 genotype. S1 strains were significantly more prevalent among patients with PUD as compared to the NUD (p < 0.05). In regard to the middle region, 55% of the patient isolates belonged to the m2 genotype with no correlation to disease. The s1m2 genotype was the most prevalent among all patients and significantly correlated with the PUD group (p < 0.05).     

Comparison of three stool antigen tests for Helicobacter pylori detection

BACKGROUND: Active Helicobacter pylori infection can be diagnosed by invasive (biopsy based) or non-invasive methods, such as stool antigen testing. AIMS: To compare three stool antigen enzyme immunoassay kits--Premier Platinum Hp SA, FemtoLab Cnx, and Hp Ag--with biopsy based methods for the detection of H pylori in previously undiagnosed patients. METHODS: One hundred and eleven adults with dyspepsia referred for endoscopy provided a stool sample for testing and had biopsies taken. Patients were considered H pylori positive if two out of three invasive tests were positive or if culture alone was positive. RESULTS: The sensitivities and specificities of the Premier Platinum Hp SA, FemtoLab Cnx, and Hp Ag stool antigen kits when compared with biopsy based diagnosis were, 63.6%, 88.0%, and 56.0% and 92.6%, 97.6%, and 97.6%, respectively. CONCLUSIONS: FemtoLab Cnx may be considered as an alternative to urea breath testing in the initial diagnosis of patients with dyspepsia who do not require immediate endoscopy. Stool testing has the potential advantages of being simple to perform, relatively cheap, and samples can be submitted directly from primary care.     

Eradication of Helicobacter pylori in clinical situations

Helicobacter pylori is prevalent worldwide, especially in developing countries, and is associated with several upper gastrointestinal diseases. Since it is present in over 90% of duodenal ulcer patients, empirical eradication in these patients is often recommended. In gastric ulcer patients, eradication is indicated only after the infection is confirmed. Testing for H. pylori infection should be carried out in patients with peptic ulcer hemorrhage, because eradication has been shown to reduce recurrent bleeding. Both H. pylori and NSAIDs are risk factors for peptic ulceration, and it is reasonable to screen for and eradicate H. pylori infection in peptic ulcer patients taking NSAIDs. H. pylori is a group I carcinogen for gastric adenocarcinoma, and should be eradicated for the primary prevention of this cancer. Eradication of this organism has been reported to result in regression of early low-grade mucosa-associated lymphoid tissue lymphoma. The role of H. pylori infection in the causation of gastroesophageal reflux and non-ulcer dyspepsia is not clearly established. Several tests are available for the diagnosis of H. pylori infection. These include invasive tests, such as histology, culture and urease test, and non-invasive tests, such as serology, urea breath test and stool antigen test. The choice of test is determined by clinical indication, pretest probability of infection, as well as the availability, cost, sensitivity and specificity of the test. H. pylori eradication therapy using proton pump inhibitor with clarithromycin and amoxycillin for 7 days has a success rate of 85-90%. Improved living standard and sanitation are vital in the control of H. pylori transmission and infection. Future development may include the use of vaccines against H. pylori, and therapies specifically targeting cagA strains of the bacteria.     

Application of a stool antigen test to evaluate the incidence of Helicobacter pylori infection in children and adolescents from Tehran, Iran

Helicobacter pylori infection is acquired mainly in childhood, especially in developing countries, where a low-cost, rapid diagnostic technique which is reliable for all age groups may be useful for the management of H. pylori infection. For this purpose, we used an HpSA test (Equipar) to detect H. pylori infection in children and adolescents from Tehran, Iran. Thirty-five children who were positive or negative for H. pylori infection by endoscopy-based tests were used as positive and negative controls for the HpSA test. Stools were collected from 430 randomly selected children and adolescents (4 to 18 years old) from southwest, near the center, and northwest of Tehran. A questionnaire that included presence of recurrent abdominal pain (RAP), family history of infection and/or peptic ulcer disease (PUD), and income of parents was completed. A good agreement was found between the results of endoscopy-based tests and those of the HpSA test; the sensitivity and specificity of the Equipar-HpSA test were 100% and 83.4%, respectively. Among 430 children and adolescents, 47% were positive by the HpSA test, of whom 82% had RAP. No difference in incidence was observed between the two sexes; the various categories of age showed an increasing incidence, ranging from 24% (ages 4 to 6) to 58% (ages 16 to 18). The rate of infection in children and adolescents from the southwest was significantly higher (70%) than the rate in those from the northwest (32%), and a family history of H. pylori infection or PUD was observed in 59% of the HpSA positive subjects. The HpSA test is a useful test to detect H. pylori infection in children and adolescents from developing countries.     

The Utility of the helicobacter pylori stool antigen test in managing dyspepsia: an experience from a low resource setting

Background

Dyspepsia is defined as a chronic or recurrent pain or discomfort centered in the upper abdomen. Endoscopy is the best strategy for confirming the cause of dyspepsia. Non- invasive strategies would be more appropriate in low resource countries where endoscopy is not readily available. However, there is concern that these strategies may miss serious disease like gastric cancer. One test that needs to be assessed in this regard is the Helicobacter pylori stool antigen test (HPSAT).

Objective

To determine the validity of the stool antigen test in predicting H. pylori associated disease among patients with dyspepsia.

Methods

In this prospective study patients with dyspepsia attending Mulago Hospital were recruited consecutively. Helicobacter pylori was determined using the Rapid Strip HpSA ®, endoscopy and gastric mucosal biopsy were done.

Results

167 patients with dyspepsia were recruited into the study. There were ninety six (57.5%) females and seventy one (42.5%) males with an average age of 48.1(±18.1) years. Patients presenting with dyspepsia in Mulago hospital were more likely to come from the Central 60 (36%) and western tribes 55 (33%). The commonest endoscopic finding was oesophagitis 25 (15%). Peptic ulcer disease was found in 32 (19.2%) and 54 (32.3%) had normal endoscopy findings. H pylori was found in 33.5% and 32.5% using the HPSAT and histology respectively. The validity of the HPSAT in predicting H.pylori associated diseases was generally low with an overall sensitivity of 55.8%, and specificity of 74.2%. However, the validity was higher in predicting the diagnosis of peptic ulcer disease with a sensitivity 59.4% and specificity 72.6%.

Conclusion and recommendations

The HPSAT may be used in the test and treat strategy for young patients with dyspepsia without alarm signs and symptoms in low resource settings. However, because of its low validity in predicting H.pylori associated disease, it is important to follow up patients so that if symptoms persist or recur endoscopy is performed     

Helicobacter pylori infection in sickle cell disease

Abdominal pain is a common presenting symptom in adults with sickle cell disease (SCD). One case of Helicobacter pylori gastritis has been reported in a child with sickle cell anemia. H. pylori-induced peptic ulcer disease (PUD) has not previously been reported in adults with SCD. We report eight cases of H. pylori infection in adult sickle cell patients presenting with acute or recurrent abdominal pain and/or gastrointestinal bleeding. In all cases, H. pylori serology (IgG) was positive, and three patients had gastric or duodenal ulcer by endoscopic examination. All patients responded to H. pylori treatment with complete resolution of symptoms by 4 weeks. The prevalence of H. pylori infection in SCD is unknown, but patients may be at increased risk for H. pylori-induced PUD and complications due to pre-existing anemia, increased nonsteroidal anti-inflammatory drug use, and alloimmunization which may delay necessary transfusion. It is important that the differential diagnosis of abdominal pain in adults with SCD include nonsickle cell-related disorders such as PUD. When confirmed, a definitive etiology of PUD must be determined so that appropriate treatment strategies can be initiated promptly and excess morbidity avoided.     

Role of ELISA in H. pylori detection and its correlation with urease test

Helicobacter pylori is one of the most common chronic bacterial infection in humans linked to acid peptic diseases, gastric carcinomas and lymphomas. The bacilli produces large amounts of urease and this property has formed the basis of detection of H. pylori by the Christensen's urease test. Where endoscopy is not clinically indicated, serology may be used to establish the diagnosis. This study was undertaken to diagnose H. pylori with the help of Christensen's urease test on endoscopic biopsy specimens & correlated with the detection in Sera, of IgG antibodies against H. pylori, by ELISA technique. The study was conducted on 100 patients suffering from acid peptic disorders out of which 40 (40%) tested positive for H. pylori both by urease and serology. Christensen's urease and ELISA were found to have sensitivities of 85.7% & 90.9% and specificities of 96% and 87.5% respectively. Christensen's urease was taken as a standard method of diagnosis and its correlation with ELISA worked out to (+1) which meant there was a strong positive association between both the tests. Hence either test could be used for primary diagnosis of H. pylori instead of histopathological study and/or culture of H. pylori.     

Detection of serum antibodies to CagA and VacA and of serum neutralizing activity for vacuolating cytotoxin in patients with Helicobacter pylori-induced gastritis.

Thirty patients with dyspepsia, with histological diagnosis of gastritis, and with endoscopic diagnosis of peptic ulcer disease (PUD) (n = 13) or nonulcer dyspepsia (NUD) (n = 17) were admitted to the study. Helicobacter pylori vacuolating cytotoxin-producing strains (Tox+) were isolated from 14 (46.7%) patients, whereas non-cytotoxin-producing (Tox-) H. pylori strains were isolated from the remaining patients. Of 30 patients studied, 20 (66.7%) had serum cytotoxin neutralizing activity in vitro. Fourteen patients with Tox+ H. pylori strains showed serum cytotoxin neutralizing activity and serum immunoglobulin G (IgG) and IgA antibodies reactive with both 87-kDa H. pylori vacuolating cytotoxin (VacA) and 128-kDa cytotoxin-associated gene product (CagA) by immunoblotting using native enriched preparations of VacA and CagA proteins from H. pylori culture supernatants as the antigens. A 94-kDa antigen cross-reacting with the 87-kDa VacA protein could be demonstrated in culture supernatant with immune sera from humans and animals. All patients (n = 10) lacking serum neutralizing activity were also negative for IgG or IgA against VacA antigen, whereas 6 of the 10 patients showed IgG serum antibody responses against CagA antigen. The prevalence of antibodies to VacA and CagA antigens was significantly (P < 0.001) higher in patients with gastritis (20 and 26 patients for VacA and CagA, respectively, of 30 patients) than in H. pylori culture-negative controls (0 of 27 for both VacA and CagA) and in randomly selected blood donors (17 and 21 for VacA and CagA, respectively, of 120 subjects). All patients with PUD had antibodies to CagA, whereas 13 of 17 (76.5%) patients with NUD had anti-CagA antibodies. Serum IgG antibodies to VacA were present in 9 (69.2%) patients with PUD of 13 patients and in 11 (64.7%) patients with NUD of 17 patients. Anti-CagA antibodies seemed to correlate better with PUD than anti-VacA antibodies.     

Diagnostic accuracy of a rapid whole-blood test for detection of Helicobacter pylori.

In this study, we evaluated a rapid whole-blood test, BM-test Helicobacter pylori, for detection of H. pylori infection in 144 and 48 patients with other gastrointestinal symptoms and with gastric cancer, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the test correlated well with the standards used for the calculation, i.e., serology by enzyme-linked immunosorbent assay or culture and histology.     

Non-invasive techniques for the diagnosis of Helicobacter pylori infection

Helicobacter pylori infection can be diagnosed by invasive techniques requiring endoscopy and biopsy (histologic examination, culture, polymerase chain reaction), and non-invasive techniques (serology, urea breath test, urine or blood, detection of H. pylori antigen in stool specimen). However, recent studies have demonstrated that a strategy of 'testing and treating' 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 non-invasive testing in dyspeptic patients followed by treatment of H. pylori in primary care based on clinical and economic analyses. Several non-invasive tests are currently available on the market. The choice depends on the clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy, and, finally, the availability of the tests. Nevertheless, two non-invasive tests are commonly used: the urea breath test, and the stool antigen test.     

Equally high prevalences of infection with cagA-positive Helicobacter pylori in Chinese patients with peptic ulcer disease and those with chronic gastritis-associated dyspepsia.

Approximately 60% of Helicobacter pylori isolates in the Western world possess the cytotoxin-associated gene A (cagA). cagA-positive H. pylori is found to be associated with peptic ulcer disease (PUD) and gastric adenocarcinoma. To investigate the cagA status of H. pylori isolates from Chinese patients with PUD and chronic gastritis (CG), H. pylori populations from 83 patients, 48 with PUD and 35 with CG, were assessed by two different cagA-specific PCRs, Southern blotting, and colony hybridization. The combined results from PCR, Southern blotting, and colony hybridization indicate a prevalence of cagA-positive H. pylori isolates of 98% (47 of 48) among Chinese PUD patients and 100% (35 of 35) among Chinese CG patients. Amplification with primer sets 1 and 2 yielded 52 and 95% of the 82 cagA-positive Chinese H. pylori, respectively. In contrast, the sensitivity of cagA-specific PCR for cagA-positive H. pylori isolates from Dutch patients with primer set 1 was 92% (112 of 122) and that with primer set 2 was 91% (50 of 55). The prevalence of cagA-positive H. pylori populations in Chinese patients with PUD and CG is almost universally high. Therefore, cagA cannot be used as a marker for the presence of PUD in Chinese patients. Our data further suggest that allelic variation in cagA may exist and that distinct H. pylori genotypes may circulate in China and Western Europe.     

Accuracy of serology for the diagnosis of Helicobacter pylori infection--a comparison of eight kits.

AIMS: To determine the accuracy of eight commercially available kits for the serological diagnosis of Helicobacter pylori infection, and hence whether a serology service could be introduced to reduce endoscopy workload. METHODS: Eighty four patients newly presenting to their general practitioners with dyspepsia were recruited. Gold standard diagnosis of H pylori infection was obtained both by a histological examination of gastroduodenal biopsy specimens and by the 14C-urea breath test (UBT). The performance of six quantitative and two qualitative enzyme linked immunosorbent assays for H pylori IgG, used according to the manufacturers' instructions, with serum samples obtained during the endoscopy visit, were compared. RESULTS: The study population had a median age of 45 years, and the prevalence of H pylori infection was 35%. With one exception, where the patient had received a course of anti-H pylori treatment between endoscopy and UBT, there was 100% concordance in the results of the two gold standard techniques. Discordant serology results were more common in patients aged > 50 years (42% of the total) than in younger patients (21%), and this was most noticeable in uninfected patients. The sensitivity of the kits was good (90-100%), but specificity was more variable (76-96%), and the rate of equivocal results was unacceptably high in some cases (0-12%). The overall accuracy of the kits ranged from 83 to 98%. Two kits in particular performed well (Pylori-Elisa II, Bio-Whitaker and Premier, Launch; qualitative) with 98% and 100% accuracy, respectively. CONCLUSIONS: In a symptomatic population with a prevalence of H pylori infection of 35%, particularly in patients aged < 50 years, some but not all serology kits may be used as a highly accurate and inexpensive alternative to the gold standard techniques.     

PCR-based restriction pattern typing of the vacA gene provides evidence for a homogeneous group among Helicobacter pylori strains associated with peptic ulcer disease

The results of PCR-based molecular typing of Helicobacter pylori strains by restriction fragment length polymorphism analysis of a 1, 161-bp nucleotide sequence of the midregion of the vacA gene are reported. A total of 48 H. pylori strains isolated from gastric biopsy specimens obtained from 18 patients with peptic ulcer dyspepsia, 15 patients with nonulcer dyspepsia, and 15 asymptomatic H. pylori-infected subjects were studied. Highly heterogeneous restriction patterns were obtained by digestion of PCR products with SauII, BglII, and HhaI, whereas HaeIII digestion resulted in a strictly homogeneous profile for H. pylori strains isolated from 14 of 18 (77.7%) patients with peptic ulcer dyspepsia, but a strictly homogeneous profile was found for strains from only 8 of 15 (53.3%) patients with nonulcer dyspepsia (P = 0.163) and 5 of 15 (33.3%) asymptomatic H. pylori-infected subjects (P = 0.014). A potentially important aspect of the results obtained is the clinical relevance, since a single restriction pattern seems to be able to identify the majority of H. pylori strains associated with peptic ulcer disease.     

Evaluation of enzyme immunoassay for detection of salivary antibody to Helicobacter pylori.

The Helisal test is a quantitative enzyme immunoassay for the measurement of Helicobacter pylori-specific immunoglobulin G antibodies in saliva. This test was evaluated in comparison with culture and histopathologic examination of gastric biopsy specimens obtained from 195 patients who underwent 200 endoscopic procedures for the investigation of gastrointestinal symptoms. Forty-one (21%) patients were found to have peptic ulcer disease, and one other patient had a gastric carcinoma. H. pylori was detected in gastric biopsy specimens obtained from 98 (49%) of the procedures. The sensitivity, specificity, and positive and negative predictive values of the Helisal test were 81, 75, 76, and 80%, respectively. The test was negative for 16 (38%) of the 42 patients with peptic ulcer disease or a gastric malignancy diagnosed at endoscopy. These results suggest that the Helisal assay is only moderately accurate for the detection of H. pylori infection in symptomatic patients.     

Histology compared with chemical testing for urease for rapid detection of Helicobacter pylori in gastric biopsy specimens.

Gastric biopsy specimens from 283 patients with ulcer and non-ulcer dyspepsia attending five gastroenterology clinics in the northern region of the United Arab Emirates (UAE) were tested by the agar gel test (n = 115) or the ultra-rapid endoscopy room test (n = 168) for the presence of Helicobacter pylori urease. Results were compared with a histological technique using the Romanowsky type (Diff-3) stain for detecting H pylori in both antral and body type gastric mucosa. A sensitivity of 94% and specificity of 100% using the agar gel test compared with 87% sensitivity and 99.3% specificity for the ultra-rapid endoscopy room test. Grading of H pylori in gastric biopsy specimens showed that the higher the histological grade, the more likely that the urease test would be positive. Both forms of urease tests have high specificity for detecting H pylori in gastric biopsy specimens, although the urea agar test has a higher sensitivity than the ultra-rapid test. Low numbers of H pylori in gastric biopsy specimens are the most important determinant of a false negative urease test.     

A 2-year study of Helicobacter pylori in children.

From September 1990 to October 1992, Helicobacter pylori was searched for in 426 children, 2 days to 16 years old, requiring upper fibroscopy for various symptoms. H. pylori was detected in 77 children (18.1%). Recurrent abdominal pain was present in 63.3% of the patients with H. pylori versus 48.6% of a control group of 74 age-matched children negative for H. pylori, weight loss was present in 6.5% of the patients versus 0% of the control subjects, and a family history of peptic ulcer was present in 14.2% of the patients versus 5.4% of the controls. Micronodular gastritis was observed in 31 children with H. pylori infection (40.2%). Among the 24 children (31.1%) with H. pylori infection and a normal mucosa at endoscopy, 18 (75%) complained of recurrent abdominal pain. H. pylori was also found in 21 of 38 children (55.2%) being examined because of short stature. These findings indicate that H. pylori should be looked for in children with recurrent abdominal pain with or without weight loss or a family history of peptic ulcer. Its relevance in short-stature syndrome requires further clarification.     

Histology of chronic gastritis with and without duodenitis in patients with Helicobacter pylori infection.

AIM: To compare the histological characteristics of Helicobacter pylori positive chronic gastritis in patients with and without associated duodenitis. METHODS: Gastric mucosal biopsy specimens were obtained from patients undergoing endoscopy for dyspepsia. Severity of gastritis and density of H pylori infection were graded according to the Sydney system. RESULTS: Of the 69 patients studied, 15 had normal histology, 22 had chronic gastritis only (77.3% H pylori positive), 21 had duodenitis (90.5% H pylori positive), and 11 had other diagnoses. In the H pylori positive patients, the median gastritis score was higher in the duodenitis group (6, range 3-9) than in the chronic gastritis only group (5, range 2-8), because of greater neutrophil activity scores in patients with duodenitis (median score 2 v 1). There were no differences in the density of H pylori infection, inflammation, atrophy, or intestinal metaplasia between patients with chronic gastritis only and those with duodenitis. CONCLUSIONS: These results suggest that H pylori positive patients with duodenitis have a more severe form of gastritis than those without associated duodenal inflammation. This is because of increased neutrophil activity, which seems to be independent of the density of H pylori infection.