Stool submission data to help inform population-level incidence rates of enteric disease in a Canadian community.

Laboratory-based surveillance data is essential for monitoring trends in the incidence of enteric disease. Current Canadian human enteric surveillance systems report only confirmed cases of human enteric disease and are often unable to capture the number of negative test results. Data from 9116 hospital stool specimens from the Waterloo Region in Canada, with a mixed urban and rural population of about 500 000 were analysed to investigate the use of stool submission data and its role in reporting bias when determining the incidence of enteric disease. The proportion of stool specimens positive for Campylobacter spp. was highest in the 15-29 years age group, and in the 5-14 years age group for Salmonella spp. and E. coli O157:H7. By contrast, the age-specific incidence rates were highest for all three pathogens in the 0-4 years age group which also had the highest stool submission rate. This suggests that variations in age-specific stool submission rates are influencing current interpretation of surveillance data.

Helicobacter pylori eradication in Western Australia using novel quadruple therapy combinations.

BACKGROUND: Helicobacter pylori eradication rates with standard triple therapy are declining worldwide. The optimal management of H. pylori is evolving and new treatment combinations for antibiotic resistant H. pylori strains are required, especially for patients with penicillin allergy. AIM: To review the effectiveness of alternative antibiotic combinations and necessity of pre-antibiotic sensitivity testing. METHODS: A total of 310 consecutive patients who had failed at least one course of standard 7-day triple therapy initially prescribed by their physicians were included in this study between year 2007 and 2011. Antibiotics were prescribed based on pre-antibiotic sensitivity tests and, if any, patient's allergy to penicillin. RESULTS: In 98.7% of the patients' samples, H. pylori was successfully cultured. The proportion resistant to clarithromycin and metronidazole was 94.1% and 67.6% respectively, with 65% resistant to both. For the in-house primary quadruple therapy, with Proton pump inhibitor, Amoxicillin, Rifabutin and Ciprofloxacin (PARC), H. pylori was successfully eradicated in 95.2% of patients. For patients allergic to amoxicillin, an alternative quadruple therapy using Proton pump inhibitor, Bismuth subcitrate, Rifabutin and Ciprofloxacin (PBRC) gave an eradication rate of 94.2%. Patients needing alternative salvage therapy were given novel personalised combinations consisting of bismuth, rifabutin, tetracycline or furazolidone; the eradication rate was 73.8%. CONCLUSIONS: Patients who present with antibiotic resistant H. pylori can be confidently treated with PARC, PBRC or other personalised salvage therapies. These regimens can be used when treatment options are limited by penicillin allergy. Pre-treatment H. pylori antibiotic sensitivity tests contributed to the high eradication rate in this study.

Shielding for a cyclotron used for medical isotope production in China.

Monte Carlo and discrete ordinate calculations have been performed to determine the doses at several locations in a positron emission tomography (PET) facility in China, where the radiation source is a cyclotron that is used for the production of the isotopes necessary for PET scans. The energy-dependent neutron source term is obtained by calculations using the ALICE code, and is interpolated for input to Monte Carlo and discrete ordinate calculations. The building that houses the cyclotron has a labyrinth of walls to minimise dose to operators and to other occupants of the building. Unbiased Monte Carlo calculations did not converge after more than one week of CPU time, whereas direction biasing alone resulted in convergence in several days. A study of several biasing techniques indicated that about a factor of 3 in computational efficiency is obtained using evaluated biasing methods. The use of adjoint fluxes for biasing Monte Carlo calculations can improve computational efficiencies by one or two orders of magnitude for some problems.

Human recombinant lactoferrin is ineffective in the treatment of human Helicobacter pylori infection.

BACKGROUND: Lactoferrin, a multifunctional glycoprotein, is known to have anti-microbial actions. Bovine lactoferrin and recombinant human lactoferrin have been shown to inhibit Helicobacter pylori, and more recently recombinant human lactoferrin was found to significantly increase the eradication rate of H. pylori when added to standard triple therapy. AIM: To determine the efficacy, safety and tolerability of recombinant human lactoferrin as a therapy in suppressing or eliminating H. pylori infection in subjects with minimal upper gastrointestinal symptoms who have not previously been treated. SUBJECTS AND METHODS: Nine healthy subjects with minimal upper gastrointestinal symptoms and a positive urea breath test were recruited. None of the volunteers had previously been treated for H. pylori. Subjects received 5 x 1.0 g human recombinant lactoferrin daily for 5 or 14 days. Breath tests were repeated during therapy and shortly after to check for eradication. The safety and tolerability of the drug were assessed by physical examination, by monitoring adverse events, and clinical laboratory evaluation. RESULTS: No conversion of the urea breath test from positive to negative was observed and there was no consistent change in urea breath test count to indicate a possible suppression of H. pylori. CONCLUSION: Lactoferrin, given as a single agent, does not eradicate H. pylori infection.

Helicobacter pylori is not the cause of sudden infant death syndrome (SIDS).

OBJECTIVES: The cause of sudden infant death syndrome (SIDS) is unknown, but our previous hypothesis proposed that Helicobacter pylori could be a causative organism. In this study, we aimed to test this hypothesis by examining gastric and tracheal tissues from a prospective cohort of SIDS infants and re-examining previously studied paraffin-fixed tissues for H. pylori. METHODS: Fresh gastric antral and trachea specimens obtained at postmortem from nine consecutive new cases of SIDS in Perth, Western Australia were studied prospectively. Tissues were evaluated for H. pylori by rapid urease test (CLOtest), bacterial culture, histology (hematoxylin and eosin, Warthin-Starry Silver, and immmunoperoxidase staining), and polymerase chain reaction (PCR). The latter two tests were also used for the re-examination of paraffin-embedded specimens from infants who died from SIDS (n = 17) and other non-SIDS causes (n = 7) in Kansas City, Missouri. RESULTS: Specimens from nine consecutive SIDS infants in Western Australia showed no evidence of H. pylori by any analyses. In the paraffin-embedded gastric and trachea specimens from Missouri, rod and coccoid-shaped bacteria were seen histologically in 33.3% of the specimens, but these were not typical H. pylori. Upon analysis by PCR, "H. pylori DNA" was detected in 53% (9/17) of SIDS samples versus 57% (4/7) in non-SIDS samples. In all cases the immunoperoxidase stain was negative, suggesting that PCR either 1) gave false positive results in this type of potentially contaminated postmortem specimen or 2) H. pylori DNA was indeed present but not increased in prevalence in SIDS infants. CONCLUSIONS: H. pylori is unlikely to be an etiological agent in SIDS.

Gastritis and gastric cancer. Western countries.

Helicobacter pylori infection is the cause of chronic gastritis that progresses to atrophic gastritis over years and decades in more than half of affected individuals. H. pylori gastritis and, particularly, subsequent atrophic gastritis increase the risk for gastric cancer on multifactorial basis. Largely unknown cascades of manifold reactions result in gene errors of epithelial cells in gastric and atrophic stomach, which raise the likelihood of gastric neoplasias and cancer among people infected by H. pylori. The prevalences and incidences of gastric cancer and H. pylori are similarly decreased during the past decades in western countries, supporting the view that H. pylori infection is a key event and a trigger of the phenomena that result in cancer in some of the infected subjects.

Culture of Helicobacter pylori from a gastric string may be an alternative to endoscopic biopsy.

Helicobacter pylori was isolated from a swallowed string from 32 of 33 adult subjects (97%) with selective culture media. With this method, antibiotic susceptibility testing and molecular epidemiology studies of H. pylori can be carried out without the need for the collection of specimens by endoscopic biopsy.

How to treat Helicobacter pylori. First-line, second-line, and future therapies.

Numerous trials were performed in the 1990s to define the optimal therapy for Helicobacter pylori infections. The proposed proton-pump inhibitor (PPI)-based and ranitidine bismuth citrate (RBC)-based triple therapies led to satisfactory results. Their first drawback is cost, and, for this reason, many people worldwide cannot benefit from these regimens. Failures of first-line therapies essentially are because of antimicrobial resistance, which increases with the selection pressure resulting from the use of these drugs. Second-line treatments using antimicrobial agents for which H. pylori resistance is low or nonexistent are being tested to find alternatives to the quadruple therapy. There is a need for new drugs, which should be highly effective, nonselective of resistant strains, and without side effects, to improve current regimens. These drugs may be the results of postgenomic studies.

Accurate diagnosis of Helicobacter pylori. Serologic testing.

Serologic testing is a useful noninvasive testing strategy for H. pylori. It is particularly useful in areas where the prevalence of H. pylori is high and inexpensive point-of-contact fingerprick tests are used. Sensitive tests are valuable ways of excluding H. pylori infection and can be used in conjunction with a direct test (urease histology culture or breath test) to confirm absence of H. pylori if the two methods are concordant. Serologic testing is more definitive and differentiating if the antigenic epitopes of H. pylori can be differentiated based on the antigenic epitopes that specifically associate with gastric cancer, peptic ulcer, and nonulcer dyspepsia. A study by Kawahara's group reported that Hsp 60 may be involved in the development of mucosa-associated lymphoid tissue based on ELISA. The idea of differentiating antigens for H. pylori may open a new area for use of serologic testing in the diagnostic approach of H. pylori infections.

Accurate diagnosis of Helicobacter pylori. Urease tests.

Because of their ease of use, rapidity, and cost-effectiveness, rapid urease biopsy tests continue to be an important diagnostic tool for the endoscopist. Various forms of these tests are available in different parts of the world, characteristically leading to sensitivities of 93% to 97% and specificities of 98%. When performing rapid urease tests, the endoscopist should be aware of factors that might lead to false-negative and false-positive results and should ensure that the biopsy specimens are of adequate size and taken from the correct location.

Successful recovery of H. pylori from rapid urease tests (CLO tests).

OBJECTIVE: Culture of Helicobacter pylori (H. pylori) and the determination of its antibiotic susceptibility is of increasing importance with the rise in numbers of antibiotic-resistant strains. The aim of this study was to determine whether H. pylori could be successfully isolated from antral biopsies used in Rapid Urease Tests (CLOtests) in clinical practice. METHODS: Antral biopsies from patients undergoing endoscopy were inserted into the gel of CLOtests to determine the H. pylori status of the patients. If the CLOtest was positive at the end of the endoscopy session, it was kept at ambient temperature until processed. In the laboratory, biopsies were removed from the gel and cultured on selective and nonselective media. In an attempt to enhance the recovery rate of H. pylori, a subset of positive CLOtests were kept at 4 degrees C from the time that the color change was noted until the removal of the biopsy. RESULTS: One hundred and forty-one positive CLOtests were studied at times between 1 h and 6 h postendoscopy. Culture success was 93% in the 1st hour but fell off sharply after 2 h (p < 0.001). Isolation was also improved if positive CLOtests were stored at 4 degrees C and plated out within 4 h (p < 0.001). CONCLUSIONS: H. pylori can be successfully cultured from biopsies in CLOtests kept at room temperature within 2 h or within 4 h if kept at 4 degrees C. Thus the antral biopsy in the CLOtest can be usefully retrieved when, in the light of the CLOtest result, the physician wishes to obtain both culture and antibiotic sensitivity results.

Usefulness of serological IgG antibody determinations for confirming eradication of Helicobacter pylori infection.

OBJECTIVE: Prior studies have suggested that IgG antibody titers may be useful to confirm successful treatment of Helicobacter pylori (H. pylori) infection. However, the diagnostic value of decreasing IgG titers is limited by the necessity to perform pre and posttreatment tests in parallel which requires stored sera. Our objective was to assess the accuracy of IgG antibody titers using the HM-CAP IgG EIA kit (Enteric Products) in monitoring treatment of H. pylori infection and to compare the relative accuracy of parallel versus serial determinations. METHODS: The 14C urea breath test (UBT) was used to confirm H. pylori infection in 83 dyspeptic patients and eradication of the organism at 4 wk and 6 months posttreatment. IgG titers pretherapy and 6 months posttherapy were determined either serially (separate EIA plates) or in parallel (same EIA plate), and the relative percent decline in antibody titer was calculated. RESULTS: When a decline of > or = 25% at 6 months was used as the cut-off for H. pylori eradication, mean sensitivities of serial and parallel determinations were 87.5% and 86.8%, respectively, and mean specificities of both were 100%. In 68 of 75 patients in whom the organism was eradicated, the mean decrease in IgG titer at 6 months was 41.1% for serial determinations and 41.5% for parallel determinations. CONCLUSIONS: Serial or parallel IgG titers offer equivalent diagnostic accuracy for confirming H. pylori eradication after therapy. A > or = 25% decline in titer 6 months after therapy is a sensitive and specific marker for eradication of the infection. Serial evaluation of IgG titers does not require serum storage, and is a cost-effective and accurate alternative to the UBT or endoscopy-based methods.

Scope and consequences of peptic ulcer disease. How important is asymptomatic Helicobacter pylori infection?

H pylori infection is so common as to seem ubiquitous in many areas of the world. Transmission is believed to be primarily person to person. The pathogen invariably damages the gastric mucosa, resulting in both structural and functional abnormalities. It causes histologic gastritis and is critical in the pathogenesis of the gastritis-associated diseases, namely, gastric ulcer, duodenal ulcer, gastric adenocarcinoma, and primary gastric lymphoma. Elimination of the infection results in healing of gastritis and cure of peptic ulcer disease.

Recognizing peptic ulcer disease. Keys to clinical and laboratory diagnosis.

An algorithmic approach to evaluation of dyspepsia or abdominal discomfort begins with differentiation between peptic ulcer disease and gastroesophageal reflux disease as well as recognition of alarm signs and symptoms for gastric cancer, which are indications for early endoscopy. In the absence of alarm symptoms, most patients should undergo noninvasive testing for H pylori infection with a serologic, urea breath, or stool antigen test. Factors to consider in selection of appropriate testing include reliability, specificity, sensitivity, cost, and local access and expertise. As a general rule, physicians should choose a test that has the best accuracy for the level of testing expertise available. The basic principle underlying testing for H pylori is that patients should not undergo testing unless the physician is willing to treat on the basis of a positive test result. In patients who receive treatment, confirmation of cure is important for preventing further morbidity and reducing risk of transmission of infection.

Practical advice on eradicating Helicobacter pylori infection.

Peptic ulcer disease associated with H pylori infection is curable. The important factors in selecting therapy are efficacy of eradication, prevention of resistance, avoidance or minimization of adverse effects, patient compliance, and cost. The most effective regimens include a bismuth preparation or antisecretory drug (proton pump inhibitor or H2 receptor antagonist) plus two antibiotics administered for 14 days. Dual-drug therapies are not recommended. Triple-drug regimens are more likely to eradicate H pylori and less likely to generate resistant strains among surviving organisms. In general, cure of the infection should be confirmed 4 weeks after completion of the treatment. Antibiotic resistance is an important consideration in choosing therapy, and patients should be taught the importance of compliance. When treatment fails, antibiotic combinations should not be repeated. Considerations for anti-H pylori treatment in a managed care environment mirror those for good medical practice in general, with special attention to stringent cost-control or outcomes-driven measures.