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Management of Helicobacter pylori infections
© The Author(s). 2016
Received: 22 December 2015
Accepted: 21 July 2016
Published: 12 August 2016
Infection with Helicobacter pylori is associated with severe digestive diseases including chronic gastritis, peptic ulcer disease, and gastric cancer. Successful eradication of this common gastric pathogen in individual patients is known to prevent the occurrence of peptic ulcer disease and gastric cancer.
With half of the world’s population being infected with H, pylori and only few antibiotics result in an effective eradication, a successful antibiotic driven worldwide eradication program seems unlikely. In addition, H. pylori eradication is not always beneficial as it has been described that eradication can be associated with an increased frequency of other disorders such as pediatric asthma, inflammatory bowel diseases and Barrett’s Esophagus. We have to accept that eradication of this infection is a two-edged sword that is both useful and harmful and we should therefore focus our H. pylori eradication policy toward selectively identify and destroy only the virulent strains.
In order to still be able to effectively treat H. pylori infections in the future we need an alternative diagnostic/treatment algorithm. This would involve a shift towards more precise and enhanced disease predicting diagnosis that tries to identify patients with chance of developing severe diseases such as gastric cancer, rather than the current regime that is geared towards find and destroy all H. pylori.
While many diagnostic tests for detecting H. pylori are expensive and/or time consuming, our above suggestion to apply molecular detection will probably not get much support. Especially since currently when treating H. pylori infections more and more eradication therapies are being prescribed without testing for antimicrobial sensitivity in order to save costs . Effectively this means that often a combination therapy is prescribed without propper sensitivity testing. Due to increased resistance rates this may in fact effectively boil down to prescribing monotherapy. We know that in those cases treatment will not only be less effective, but in fact favors the generation of resistance to the one drug that was effective. While currently invasive procedures are still required in order to obtain material for culture and antimicrobial resistance determination, there is a now molecular method being developed that may allow for fecal matter based PCR testing for resistance against many of the commonly used H. pylori drugs [20, 21]. It will be relatively easy to also include a selection of H. pylori virulence markers in these tests, facilitating screening algorithm that would allow discriminating the good H. pylori from the bad. This would give rise to the screening and eradication scheme outlined in Fig. 1, where in principle only symptomatic patients would be treated after testing for virulence and resistance. Only anti-H. pylori therapies that can achieve eradication rate ≥90 % are considered effective, but increasing resistance hampers the efficacy of prescribed regimens [12, 21, 22]. Up to now we have taught clinicians to eradicate all cases of H. pylori infections as they would with any other pathogenic bacterial infection [23, 24]. However in the light of our current knowledge where only a minority of H. pylori infections will cause clinical symptoms screening for H. pylori and subsequent eradication may no longer be the best approach. For one, recent studies showed that asthma and other diseases can appear in the absence of H. pylori, an interesting phenomenon which complicates links between H. pylori infection and human disease [25, 26]. However we should consider occurrence of gastric cancer while it can be reduced in H. pylori infected patients through the elimination of H. pylori (either by antibiotic therapy or vaccine) [27, 28]. Current findings are indicate an association between H. pylori free individuals and certain immune malfunctional diseases including allergy and asthma [26, 29], inflammatory bowel diseases (IBS) [30, 31] and Barrett’s Esophagus (BE)  in Helicobacter free patients. One has to be aware however that this protective link between H. pylori infections and immune related disorders is not always observed and thus disputed by some authors . While infection with H. pylori will result in gastritis subsequently we should be aware that only very few infected patients, even when left untreated will actually develop gastric cancer. Basically, an Operative Link for Gastritis Assessment (OLGA)-staging system has been designed to simplify evaluation of gastric atrophy . This staging system was an updated version of Sydney system, thus, the staging system can then rank the histologic phenotypes of gastritis with a progressively increasing gastric cancer risk . Moreover, new challenge can be to develop different algorithms that would predict people with high risk of developing gastric cancer using the pathotype of the infecting strain of H. pylori. In this proposed algorithm, only virulent H. pylori strains should be targeted/eliminated, thus allowing non-virulent strains to remain in place and so that they can exert their beneficial effects. With Next Generation Sequencing (NGS) techniques slowly becoming a routine technique in human diagnostic laboratories and its prices and turn-around times rapidly falling finding and destroying only virulent H. pylori strains may soon become a viable option. The classical perception that all infections should be treated as potentially disease causing has promoted that clinicians were eager to eliminate H. pylori infections and that is why they used (or in our view perhaps massively overused) antibiotics to eradicate this infection.
Perhaps for the control of future symptoms in the currently asymptomatic H. pylori patients we should introduce a population based screen for the presence of H. pylori at age 50 using a non-invasive test like the fecal antigen test or urease breath tests to establish the presence of a H. pylori infection (Fig. 1) . For those positive follow-up screening with either non-invasive molecular test that establishes the virulence of the infecting strain (see above), and/or a serologic tests that would predict the status of the atrophy . If these tests would predict an increased risk of future disease development, treatment would then be indicated, and one would proceed as outlined above for the symptomatic patient. The problem of H. pylori antibiotic resistance is real and as a result, we are now confronted with a new generation of multi drug resistant H. pylori strains, for which suitable treatment options no longer exist.
Thus we may need to revise the available guidelines to include the option where the best possible treatment of an infection may no longer be geared towards blindly eradicating all infected patients (search and destroy) but be directed towards a selective eradication strategy (find and destroy only virulent strains). However this requires the implementation of effective strategies to identify virulent strains as well as awareness amongst physicians that treatment of all individual patients may severely limit the treatment options for our future patients.
BE, Barrett’s esophagus; IBS, inflammatory bowel diseases; NGS, next generation sequencing; OLGA, operative link for gastritis assessment
No funding was received for this study.
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This opinions as presented in this manuscript are the sole responsibility of the authors and do not necessarily represent the official views of any institute or organization. The contents of this manuscript are based on data available in the public domain and No patient or animals materials and/or experiments were performed for this manuscript.
A.T.B.A and J.G.K both made substantial contributions to conception and design, or acquisition of data, and analysis and interpretation of data and have been equally involved in the drafting of the manuscript and/or revising it critically for important intellectual content. Both authors gave approval of this final version of the manuscript.
All authors declare that they have no financial or non-financial competing interests.
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