Characteristics of Helicobacter pylori infection in Jamaican adults with gastrointestinal symptoms.

Helicobacter pylori infection is common in Jamaica. Describing its epidemiology in a population-based study depends largely on serology, but serologic assays have not been validated in this population. To address this issue, we examined the presence of H. pylori infection in 30 sequential adult patients with gastroduodenal symptoms by three biopsy-based methods (rapid urease test, histology, and culture) as well as by one research and two commercial enzyme-linked immunosorbent assays (ELISAs). A patient was considered H. pylori positive if the organism was detected by at least one biopsy-based method. Eighteen (60%) of the 30 patients were H. pylori positive by these criteria, whereas 21 (70%) were seropositive for H. pylori immunoglobulin G by our research ELISA. The presence of H. pylori infection in patients with gastric cancer and those with chronic gastritis was missed by biopsy-based methods but was detected by serologic assays. This observation indicates that serologic assays may be better suited for the detection of this infection in a population in which H. pylori-associated pathology is prevalent. The performance of our research ELISA in detecting biopsy-based H. pylori-positive cases was excellent, with a sensitivity and specificity of 100% and 75%, respectively. Molecular genotyping of the isolates revealed that the predominant H. pylori genotypes in this cohort of Jamaicans were cagA(+) vacA slb-m1, and iceA2. The validated serologic assay enables us to interpret epidemiologic data from population-based studies in Jamaica by comparison to those from other populations.

Admixture with whole blood does not explain false-negative urease tests.

Rapid urease test sensitivity for Helicobacter pylori is reduced in the presence of active upper gastrointestinal bleeding. The aim of this study was to evaluate the in vitro effect of whole blood on rapid urease testing. Urease solution was added to normal saline, and heparinized whole blood both positive and negative for H. pylori antibody. The mixtures were then serially diluted in saline, and/or whole blood and added to three different rapid urease kits. The admixture of urease in H. pylori-seropositive whole blood diluted in either saline or whole blood enhanced performance in both kits fourfold compared with saline alone. No false-negative results were observed in either kit. Seronegative whole blood produced similar results. Undiluted saline or whole blood produced no positive rapid urease tests. Whole blood accelerates the urease reaction in vitro. Neither H. pylori antibody-positive nor -negative whole blood adversely impacted the rapid urease test. False-negative rapid urease test results in upper gastrointestinal bleeding cannot be explained by admixture with whole blood.

Fifteen years later: colonoscopic retroflexion revisited.

OBJECTIVE: Retroflex views of the rectal vault are included in the teaching of colonoscopic technique but are not pervasive in clinical practice. The utility of adding a retroflex maneuver at the end of colonoscopy has yet to be determined. The aim of this study was to evaluate the additional benefit of a retroflex view of the rectal vault at the completion of colonoscopic examination. METHODS: A prospective study of consecutive colonoscopies performed by a single physician was conducted. The rectal vault was first visually inspected upon withdrawal of the colonoscope. The endoscope was then readvanced into the rectum and retroflexed to view the vault. Endoscopic findings on both views were recorded along with demographic patient information. The six groups of findings sought on the two views were: retained stool, abnormal hemorrhoids, erosions/ulcerations, polyps, masses, and normal examinations. A determination on whether retroflex views influenced patient diagnosis was recorded by the endoscopist. RESULTS: There were 453 patients enrolled: 182 (40.2%) male and 271 (59.8%) female, consisting of 216 African-Americans, 232 Caucasians, and five Asians. The retroflex maneuver was performed successfully in 445 of 453 patients. In all but nine cases, the retroflex view did not produce additional information. The nine findings included three inflammatory pseudopolyps, five hyperplastic polyps, and one case of erosions/ulcerations. CONCLUSIONS: In the majority of cases, retroflexing the endoscope does not produce additional information compared with the thorough examination in straight view. The retroflex view may be of benefit if there is suspicion of pathology upon insertion or withdrawal of the colonoscope.

Helicobacter pylori and gastric cancer.

Infection with Helicobacter pylori is now recognized as the primary cause of peptic ulcers and their recurrence. Compelling evidence has also been found linking H. pylori infection to gastric cancer, the second most common cancer in the world. Given the high rate of patient morbidity and mortality associated with gastric cancer, any method by which one can reduce the occurrence of the disease or increase its early detection is desirable. The strong correlation with H. pylori infection and the current availability of easily administered tests for the detection of the pathogen argue for screening at least those individuals with a family history of gastric cancer or other risk factors. This article reviews the association between H. pylori and gastric cancer and the pathologic changes that the infection produces in the gastric mucosa, as well as the cost-effectiveness of universal testing and eradication of the infection in H. pylori-positive individuals to reduce gastric cancer.

Comparison of [13C]urea blood test to [13C]urea breath test for the diagnosis of Helicobacter pylori.

OBJECTIVE: It has been determined that the [13C]urea breath test (UBT) is a safe and effective way of detecting Helicobacter pylori (H. pylori) infection. Some individuals may have difficulty performing the exhalation component of the test, possibly due to age, or mental or physical compromise. Our aim was to determine if a commercially developed [13C]urea blood test could be utilized as a substitute for the UBT to detect H. pylori infection. METHODS: Patients who were referred by their physicians for UBT were offered study inclusion. Patients underwent baseline and 30-min UBT. A simultaneous blood sample of 3 cc was drawn into a heparinized vacutainer at the 30-min period of the UBT. [13C]urea levels in both blood and breath samples were analyzed using isotope ratio mass spectrometry. UBT > or = 6 delta per mil over baseline and urea blood tests > (-17 delta per mil) were considered positive. RESULTS: One hundred sixty-one patients (68 men/93 women) with average age of 47.0 +/- 14.2 yr were tested. Agreement between breath and blood test results occurred in 153/161 (95%) cases. Using the UBT as the diagnostic standard, the urea blood test resulted in 44 true positive, 109 true negative, four false positive, and four false negative results, giving a sensitivity of 92%, specificity of 96%, positive predictive value of 92%, and negative predictive value of 96%. CONCLUSIONS: The urea blood test was found to be comparable to the urea breath test in the detection of H. pylori infection. The urea blood test will be accurate in the diagnosis of active H. pylori infection.

Evaluation of the FlexSure HP whole blood antibody test for diagnosis of Helicobacter pylori infection.

OBJECTIVE: Rapid, inexpensive, reliable tests are needed to facilitate the diagnosis of Helicobacter pylori infection. We evaluated the accuracy of the new FlexSure HP whole blood test (SmithKline Diagnostics, Inc.), a rapid, qualitative in-office test for the detection of antibodies to H. pylori utilizing whole blood obtained from a fingerstick. METHODS: Five North American sites enrolled patients not previously treated for H. pylori who underwent upper endoscopy. Patients had not received antibiotics, bismuth, or proton pump inhibitors within 4 wk before study enrollment. Bacterial infection was established by the presence of H. pylori in gastric biopsies (minimum of two) or positive rapid urease test of antral tissue. The presence of IgG antibodies was determined using FlexSure HP whole blood tests with blood obtained by fingerstick and FlexSure HP serum and ELISA (HM-CAP) tests with serum obtained from venipuncture. RESULTS: Three hundred ninety-three patients were enrolled (56% male; mean age, 46.8 +/- 16.0 yr). H. pylori infection was present in 187 (48%). Compared with the standard of histology and rapid urease test, sensitivity for FlexSure HP whole blood, FlexSure HP serum, and HM-CAP EIA were, respectively, 84%, 90%, and 95% (p < 0.05 compared with FlexSure HP whole blood). There were no statistical differences in specificity or overall accuracy between the three tests. CONCLUSIONS: FlexSure HP whole blood demonstrated an accuracy not significantly different from the FlexSure HP serum test but had sensitivity significantly lower than the HM-CAP EIA. FlexSure HP whole blood may be useful for in-office H. pylori diagnosis.

Effect of standard and high dose ranitidine on [13C]urea breath test results.

OBJECTIVE: It has been suggested that standard dose H2 blockers will affect the [14-C]urea breath test. The aim of this study was to evaluate the effect of standard and high dose ranitidine on the [13C]urea breath test in a prospective cross-over study. METHODS: Volunteers found to be positive for H. pylori by IgG serology and [13C]urea breath test were given either ranitidine 150 mg b.i.d. or 300 mg b.i.d. for 14 days. Repeat breath tests were completed on the last day of antisecretory dosing and study patients were immediately crossed over to the other ranitidine dose. The third breath test was performed at 14 days after initiation of the new dose. RESULTS: A total of 20 volunteers were enrolled. Using the established cut-off of 2.4% for the commercial breath test, only one patient developed negative results on H2 blockers. This patient had negative breath tests on both ranitidine doses and remained test-negative off all medications 6 wk after study completion, suggesting either a false positive baseline test or an unexpected bacterial eradication. No specific trend in breath test results was observed for the group (p=NS). On ranitidine 300 mg, six of 19 patients elevated their breath results from 23% to 112% (mean 76%) above baseline. CONCLUSION: Ranitidine at standard or high doses did not generate a reproducible decline in breath test results. Histamine 2 blockers do not need to be discontinued before urea breath testing.

Four-year trends in Helicobacter pylori IgG serology following successful eradication.

PURPOSE: Detection of anti-Helicobacter pylori antibodies is accurate in the diagnosis of the infection, and there is a decline in IgG titers after successful eradication. It is not known whether these titers continue to decline during the next 3 to 4 years. PATIENTS AND METHODS: Patients had been successfully treated for H pylori with triple therapy (metronidazole, tetracycline, and bismuth subsalicylate) during 1990 and 1991. Those who had frozen serum samples available from that time were contacted to have follow-up serum collected in 1994. A simultaneous [13C]urea breath test was done to confirm H pylori infection status. Serology was determined by quantitative enzyme-linked immunosorbent assay (ELISA) and qualitative immunoassay. RESULTS: All 29 patients who agreed to participate were free of H pylori infection. They had a mean decrease in H pylori IgG titers of 51% from baseline (P <0.001). Titers remained stable from 1 year to a mean of 3.5 years after therapy (range 2.8 to 4.4). Of the 29 patients, 21 (72%) remained seropositive by ELISA 3.5 years after successful H pylori treatment, and 18 (62%) remained positive by rapid serum immunoassay. CONCLUSION: IgG titers against H pylori plateau at a 50% decrease after therapy. Helicobacter pylori serology, either quantitative or qualitative, will yield false positive results in patients who have previously been treated for H pylori and should not be used to determine infection status in this population.

Cost savings in duodenal ulcer therapy through Helicobacter pylori eradication compared with conventional therapies: results of a randomized, double-blind, multicenter trial. Gastrointestinal Utilization Trial Study Group.

BACKGROUND: We hypothesized that treatment of duodenal ulcer disease with antibiotic therapy directed toward Helicobacter pylori infection is more cost-effective than therapy with antisecretory agents. METHODS: A randomized, double-blind, multicenter clinical trial of adult patients with active duodenal ulcer and H. pylori infection was conducted. Patients were randomized to receive 500 mg of clarithromycin 3 times a day plus 40 mg of omeprazole daily for 14 days followed by 20 mg of omeprazole daily for an additional 14 days (group 1), 20 mg of omeprazole daily for 28 days (group 2), or 150 mg of ranitidine hydrochloride twice a day for 28 days (group 3). The use of ulcer-related health care resources was documented during monthly interviews for 1 year after the initial therapy. Clinical success was evaluated 4 to 6 weeks and 1 year after the end of therapy. RESULTS: Of the 819 patients enrolled, 727 completed the study. Group 1 included 243 patients; group 2, 248 patients; and group 3, 236 patients. Patients in group 1 used fewer ulcer-related health care resources during the 1 year after therapy compared with groups 2 and 3 (comparisons are given as group 1 vs group 2 and group 1 vs group 3, respectively): the number of endoscopies performed, 28 vs 76 (P<.001) and vs 71 (P<.001); patients receiving drugs to treat an ulcer, 118 vs 180 (P<.001) and vs 168 (P<.001); clinic visits, 83 vs 135 (P=.05) and vs 161 (P<.001); hospitalizations, 0 vs 5 (P=.045) and vs 6 (P=.02); and length of hospital stay, 0 vs 24 days (P=.04) and vs 37 (P=.04). When ulcer-related costs were defined as the outcome variable in a multivariate linear regression analysis, therapy was determined to have a significant influence on costs (group 1 vs group 2, P<.001; group 1 vs group 3, P=.008). Clinical success rates at the end of the study and cure of H. pylori infection were significantly greater in group 1 compared with groups 2 and 3 (P<.001). Therapy with clarithromycin plus omeprazole provided savings of $1.94 and $2.96 (compared with therapy with omeprazole and with ranitidine hydrochloride, respectively) per dollar spent within the first year after therapy. This incremental cost-benefit translates to savings of $547 or $835 per patient in group 1 (compared with patients in group 2 or group 3, respectively) during the first year after therapy. CONCLUSIONS: Combination therapy with clarithromycin and omeprazole resulted in significantly fewer uses of ulcer-related health care resources than conventional antisecretory therapy during a 1-year follow-up and significant savings in associated costs during the same period. Patients who received clarithromycin plus omeprazole also showed a significantly improved clinical outcome compared with patients who received only omeprazole or ranitidine.

Accuracy and economics of Helicobacter pylori diagnosis.

Many diagnostic tests are available to establish Helicobacter pylori infection status. Most of the tests are accurate though none works perfectly, and no gold standard for diagnosis exists. Newly developed serum immunoassay kits can substitute for laboratory-based enzyme-linked immunosorbent assays, but whole blood immunoassays do not yet demonstrate adequate performance characteristics. Serologic diagnosis of H. pylori remains the most cost-effective option and should be utilized to establish initial infection in the majority of cases. If rapid urease testing is performed at endoscopy, negative results can be confirmed with a subsequent serologic test in those patients with a high probability of infection. Obtaining additional gastric tissue at endoscopy to evaluate for bacterial infection is reasonable if specimens are being taken for a mucosal defect. Confirmation of bacterial eradication cannot be justified for all post-treatment patients at present due to the expense. It is important to test for cure in those patients with complicated ulcer disease and those with recurrent symptoms after therapy.

Value of serology as a noninvasive method for evaluating the efficacy of treatment of Helicobacter pylori infection.

The systemic humoral response to Helicobacter pylori was studied in 86 infected adult patients before antimicrobial therapy and at intervals following therapy. Endoscopy with collection of biopsy specimens was performed immediately before treatment; a 13C-labeled urea breath test was performed, and blood specimens were collected before treatment and at 1, 3, 6, 9, and 12 months after treatment. Serum samples from three patient groups (eradication success [n = 50], eradication failure [n = 16], and no treatment [n = 20]) were assayed for IgA and IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Levels of antibody to H. pylori before treatment were similar in all three groups. As expected, the no treatment and eradication failure groups had no significant changes in antibody levels during the study period. In contrast, for the eradication success group, the specific IgA and IgG antibody levels decreased progressively and significantly. We conclude that serology is a potentially useful way to monitor the success of treatment of H. pylori infection without using invasive or more expensive methods.

Helicobacter pylori recurrence after successful eradication: 5-year follow-up in the United States.

OBJECTIVES: We previously reported a 3.4% posttreatment Helicobacter pylori recurrence rate over 18 months. We undertook to establish the rate of reinfection in our United States cohort up to 80 months after successful therapy. METHODS: Previously studied patients who had successful triple therapy for H. pylori during 1989-92 were identified. Baseline infection had been established by the presence of H. pylori on antral biopsies as well as positive [13C]urea breath tests. Eradication of H. pylori had been confirmed by repeat endoscopy and breath test 4 wk after therapy. Three of four subjects reported that H. pylori recurrences had occurred in the first year after therapy. Patients remaining free of infection were invited back for follow-up breath test in 1995-1996. RESULTS: One hundred fourteen patients were identified: 56 were unavailable or were using medications that would interfere with H. pylori testing. The remaining 58 patients (50.9%) included 32 M/26 F, mean age 62.9 yr. The mean follow-up period was 58 months, range 34-80 months. Positive breath tests occurred in 2/58 patients (3.4%) at 54 and 70 months after therapy. Both patients reported recurrent epigastric symptoms. The H. pylori recurrence rate for our group was 3.4% over the 4 yr since their last evaluation, or 0.85% recurrence per year. Defining recurrence as reinfection occurring after 1 yr, the total recurrence rate for the group over the 5 yr since treatment was 3/59 patients (5.1%), or 1.0% H. pylori recurrence per year posttreatment. CONCLUSIONS: The rate of H. pylori reinfection after successful therapy is low in the United States and approximates 1% per year.

Evolving therapy for Helicobacter pylori infection: efficacy and economic impact in the treatment of patients with duodenal ulcer disease.

Helicobacter pylori infection is present in most patients with duodenal ulcer disease, and cure of H pylori infection has been shown to dramatically reduce ulcer recurrence. Therapeutic strategies for duodenal ulcer disease have rapidly evolved over the past several years in an effort to consistently cure H pylori infection in a safe, cost-efficient manner. This paper reviews the effectiveness of treatments for H pylori infection in patients assessed with duodenal ulcer disease. The impact of clinical success on economic effectiveness has been determined in a recent prospective outcomes trial. Treatments with clarithromycin plus omeprazole or clarithromycin plus ranitidine-bismuth-citrate (RBC) provide consistent cure of H pylori infection, with eradication rates of 70% to 80%. Recent studies suggest that higher rates of eradication are possible with triple combination therapy (e.g., clarithromycin plus a second antibiotic and a proton pump inhibitor or RBC), but the optimal triple therapy regimen (including the combination of drugs, dosage, and duration of treatment) has not yet been defined. A recent 1-year prospective outcomes trial has demonstrated that eradication therapy with clarithromycin and omeprazole, compared with standard antisecretory therapy, provides measurable savings in utilization of ulcer-related health-care resources. Combination therapy with clarithromycin plus omeprazole, clarithromycin plus RBC, or clarithromycin plus lansoprazole and amoxicillin have been approved for the treatment of H pylori infection in patients with duodenal ulcer disease. Economic analysis has confirmed that cure of H pylori infection not only contributes to the clinical resolution of duodenal ulcer disease, but also provides economic advantages by reducing costs associated with recurrence.

Diagnostic tests for Helicobacter pylori infection.

The two major catagories of diagnostic methods for Helicobacter pylori are invasive tests, or those that require endoscopy, and noninvasive, or nonendoscopic, tests. Diagnostic tests that use endoscopy include rapid urease tests, histology, and culture. Tests for which esophagogastroduodenoscopy is not necessary include various methods of antibody detection and carbon-labeled urea breath tests. Most tests are accurate, although none works perfectly and no gold standard for diagnosis exists. This article reviews the diagnostic methods available to establish H. pylori infection status and identifies some common mistakes made in testing. The costs associated with H. pylori diagnosis are evaluated and some cost-effective approaches to testing are suggested. Finally, the article offers some guidelines on choosing the appropriate diagnostic test in different clinical situations to determine the H. pylori infection status.

Evaluation of a rapid, new method for detecting serum IgG antibodies to Helicobacter pylori.

There is an increased need for rapid, inexpensive tests to diagnose Helicobacter pylori infection. Our objective was to determine the performance characteristics of an immunochromatographic test (ICT) for detection of anti-H. pylori IgG antibodies. A commercially available ICT kit (FlexSure HP) was tested with a well-characterized cohort of banked sera as well as with fresh serum from randomly selected symptomatic patients. The ICT was evaluated with 107 stored sera and 96 prospective patients. The test correctly identified 65 of 68 H. pylori-infected and 37 of 39 noninfected stored sera and 54 of 57 infected and 30 of 39 noninfected patients. Sensitivity, specificity, and positive and negative predictive values were 96%, 95%, 97%, and 93% in stored serum and 95%, 77%, 86%, and 91% in fresh serum, respectively. We concluded that the ICT, reported at 4 min, is highly sensitive for detecting anti-H. pylori IgG antibodies in human serum. With a high negative predictive value, the test may be used to exclude H. pylori infection in symptomatic patients.

Quantitative noninvasive testing for Helicobacter pylori does not predict gastroduodenal ulcer disease.

BACKGROUND: Helicobacter pylori is strongly associated with gastric and duodenal ulcer disease. However, the diagnosis of gastroduodenal ulcers requires an endoscopic or radiographic examination. In this study, we attempted to establish a relationship between the magnitude of [13C]urea breath test results or serum H. pylori IgG levels and endoscopic findings in H. pylori-infected individuals. METHODS: Patients who had undergone endoscopy and had a positive [13C]urea breath test and/or positive H. pylori IgG serology were identified. Endoscopic diagnoses included duodenal ulcer, gastric ulcer, nonulcer dyspepsia, and others. Results of 6% or greater on the [13C]urea breath test was defined as positive for H. pylori infection. H. pylori IgG serology was determined by an enzyme linked immunosorbent assay with values of greater than or equal to 1.0 being seropositive. RESULTS: One hundred seventy-five patients were seropositive (mean = 3.01 +/- 1.58). One hundred sixty-eight patients had a positive [13C]urea breath test (mean = 25.43 +/- 16.90). One hundred fifty-five patients were common to both the groups. Statistical analysis did not reveal any relationship between quantitative [13C]urea breath test results or H. pylori IgG values and endoscopic diagnoses. CONCLUSION: The magnitude of [13C]urea breath test or H. pylori IgG serology cannot be used to predict the presence or absence of gastroduodenal ulcer disease.