Helicobacter pylori therapy: what is coming?

Despite increasing bacterial resistance to existing drugs, investment in antibacterial discovery and development efforts appears to be flagging. Several factors may play a role in depressing this important area of research, including fragmentation of the antibacterial market, patent expiry and recent confusion within the FDA over how to evaluate new antibacterial candidates. As reflected in patents published in the years 1997 versus 2002, activity in this arena is increasingly focused on novel drug classes and is shifting from large pharmaceutical firms to smaller speciality companies. While this shift favours compounds whose medical need is not matched by a blockbuster market, it may leave the field exposed to overwhelming challenges.     

Helicobacter pylori: where are we and where are we going?

This paper contains a personal view on what has been achieved in Helicobacter pylori research and what the expectations might be for further developments. Knowledge about the organism is already extensive. Particularly intriguing are the differences in genetic make-up in the various geographical regions. Sadly, detailed knowledge on how the organism spreads is still lacking. The clinical spectrum of the disease in man is largely known, but as H. pylori is disappearing worldwide, the relative frequency of H. pylori-negative ulcer disease is increasing. To what extent H. pylori disappearance and eradication is responsible for the decreasing incidence of gastric cancer remains uncertain. Antimicrobial therapy is dominated by proton pump inhibitor triple therapy as first line with quadruple therapy as second-line therapy. The long-term consequences of the rising resistance to the 'key' antimicrobials are so far unknown and speculative.     

The Choice of Proton Pump Inhibitor: Does it matter?

Proton pump inhibitors are used at different dosages for the treatment of acid-related gastrointestinal disorders, such as gastro-oesophaeal reflux and peptic ulcer disease. Comparisons of four different proton pump inhibitors: lansoprazole, omeprazole, pantoprazole, and rabeprazole show that they all have similar potency and efficacy. Rabeprazole, however, displays a slightly more rapid onset of acid inhibition than the others; the clinical advantage of this seems limited. The S-isomer of omeprazole, esomeprazole, exhibits a somewhat higher potency than the other proton pump inhibitors. Reports supporting a clinical advantage of this property are not convincing. To conclude, all inhibitors seem comparable as regards inhibition of gastric acid secretion.     

Appropriate strategies for testing and treating Helicobacter pylori in children: When and how?

Helicobacter pylori infection is acquired primarily during childhood and carries a significant lifetime risk for morbidity. In developing countries, approximately 70% of children are infected with the bacterium by their 15th birthday. In the United States, the rate of H pylori infection among children varies widely—approximately 10% of all 10-year-olds are infected; however, this figure is substantially higher among populations of immigrant children and children born of recent immigrants to the United States. H pylori transmission is primarily “person-to-person” via fecal-oral, gastric-oral, or oral-oral routes, with evidence suggesting contaminated water as a potential source of infection. Risk factors for infection in childhood include an infected family member, having ≥2 siblings, crowded living conditions, lower socioeconomic means, and attendance at a daycare facility. The natural history of H pylori infection includes an increased lifetime risk for peptic ulcer and gastric adenocarcinoma or lymphoma. In children and adults who develop H pylori–related peptic ulcer, cure of the infection is associated with a <5% rate of ulcer recurrence. The ideal mode of H pylori detection among children is unclear—currently available serology and whole blood tests are unreliable, while the urea breath test and stool antigen tests have not been studied adequately. Children with confirmed H pylori–related peptic ulcer disease, iron-deficiency (sideropenic) anemia, or a first-degree relative with gastric cancer should be treated for the infection using 1 of 3 available 10- to 14-day triple therapy regimens recommended by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.     

Test and treat or test and scope for Helicobacter pylori infection. Any change in gastric cancer prevention?

A 'test and treat' strategy is advocated for patients with dyspepsia under the age of 45 years, with endoscopy reserved for those with alarm symptoms or aged over 45 years. One of the consequences of this strategy will be a reduction in population infection rates of Helicobacter pylori. It is now clear that H. pylori is one of the prime initiators of gastric cancer with up to 70% of gastric cancers attributable to H. pylori. What remains unclear is if H. pylori reduction will lead to a reduction in gastric cancer.     

Does seropositivity for Helicobacter pylori antibodies increase outpatient costs for gastric and duodenal ulcer or inflammation?

BACKGROUND: Helicobacter pylori is regarded as an important cause of both peptic ulcer and chronic gastritis. In particular, seropositivity is highest in patients with duodenal ulcer. No studies have determined whether there are differences in the direct medical costs associated with gastric/duodenal ulcer or inflammation, between seropositive and seronegative patients. OBJECTIVE: To examine the relationship between seropositivity for H. pylori and outpatient visits and direct medical costs for gastric/duodenal ulcer or inflammation in Japan from the perspective of the payor and patients. METHODS: Participants were males (n = 653) who worked for an agricultural co-operative in Fukuoka Prefecture, attended an annual health examination (including a written lifestyle and medical survey), belonged to the same health insurance society consistently for 4 years from April 1996 to March 2000, and provided a blood sample. The survey asked about lifestyle, including smoking and drinking, and past medical history. We retrospectively analysed the annual number of outpatient visits per person and outpatient medical cost (Yen, 2000 values) per person for visits relating to gastric or duodenal ulcer or inflammation using International Classification of Diseases (9th edition) -- Clinical Modification codes. We assessed for potential confounding factors using analysis of covariance and the chi-square test. RESULTS: The annual outpatient incidence of disease, the number of visits to physicians, and the medical costs for gastric or duodenal ulcer or inflammation were about 2-fold greater in individuals with antibodies to H. pylori compared with those without antibodies. CONCLUSION: Population-based studies and/or randomised controlled clinical trials that target high-risk groups and account for the unique way in which data are collected in Japan are needed to determine whether medical costs for gastric and duodenal ulcer might be reduced by treating asymptomatic patients who have antibodies to H. pylori.     

Blue light for infectious diseases: Propionibacterium acnes,Helicobacter pylori,and beyond?

Blue light, particularly in the wavelength range of 405–470 nm, has attracted increasing attention due to its intrinsic antimicrobial effect without the addition of exogenous photosensitizers. In addition, it is commonly accepted that blue light is much less detrimental to mammalian cells than ultraviolet irradiation, which is another light-based antimicrobial approach being investigated. In this review, we discussed the blue light sensing systems in microbial cells, antimicrobial efficacy of blue light, the mechanism of antimicrobial effect of blue light, the effects of blue light on mammalian cells, and the effects of blue light on wound healing. It has been reported that blue light can regulate multi-cellular behavior involving cell-to-cell communication via blue light receptors in bacteria, and inhibit biofilm formation and subsequently potentiate light inactivation. At higher radiant exposures, blue light exhibits a broad-spectrum antimicrobial effect against both Gram-positive and Gram-negative bacteria. Blue light therapy is a clinically accepted approach for Propionibacterium acnes infections. Clinical trials have also been conducted to investigate the use of blue light for Helicobacter pylori stomach infections and have shown promising results. Studies on blue light inactivation of important wound pathogenic bacteria, including Staphylococcus aureus and Pseudomonas aeruginosa have also been reported. The mechanism of blue light inactivation of P. acnes, H. pylori, and some oral bacteria is proved to be the photo-excitation of intracellular porphyrins and the subsequent production of cytotoxic reactive oxygen species. Although it may be the case that the mechanism of blue light inactivation of wound pathogens (e.g., S. aureus, P. aeruginosa) is the same as that of P. acnes, this hypothesis has not been rigorously tested. Limited and discordant results have been reported regarding the effects of blue light on mammalian cells and wound healing. Under certain wavelengths and radiant exposures, blue light may cause cell dysfunction by the photo-excitation of blue light sensitizing chromophores, including flavins and cytochromes, within mitochondria or/and peroxisomes. Further studies should be performed to optimize the optical parameters (e.g., wavelength, radiant exposure) to ensure effective and safe blue light therapies for infectious disease. In addition, studies are also needed to verify the lack of development of microbial resistance to blue light.     

Review article: is there a link between micronutrient malnutrition and Helicobacter pylori infection?

Helicobacter pylori causes a chronic gastric infection, which is usually life-long. Many epidemiological studies have shown that this is probably one of the most common bacterial infections throughout the world involving 30% of the population living in developed countries and up to 80-90% of the population in developing regions. Concomitantly, developing regions also have high prevalence of micronutrient malnutrition. In the last few years, some studies have suggested that H. pylori infection may affect the homeostasis of different micronutrients including iron, vitamin B12, folic acid, alpha-tocopherol, vitamin C and beta-carotene. In this article, we discuss the current scientific information of the effect that H. pylori infection may produce on micronutrient malnutrition.     

Have we found the source of Helicobacter pylori?

Besides the well established Helicobacter pylori reservoir, i.e. the human stomach, numerous other sources have been hypothesized. However, none has been definitely proven. In some instances (pig, sheep), Helicobacter species closely related but different from H. pylori were detected but the results were misleading because culture of sufficiently discriminating molecular techniques were not used. In other cases, the strain was really H. pylori (cat) but the case was anecdotal or the animal species (monkey) has so little contact with humans that the possible source has no epidemiological consequence. This is also the case for houseflies which theoretically can be a vehicle, but practically speaking are not because of too few viable bacteria present in faeces. Molecular epidemiology studies demonstrating the route of transmission (faecal-oral, oral-oral or gastro-oral) are still lacking but recent studies have confirmed the presence of viable H. pylori in vomitus and in faeces in the event of diarrhoea.