Mohammad Zamani

Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection

The epidemiology of Helicobacter pylori infection is poorly understood.

Role of food in environmental transmission of Helicobacter pylori

Helicobacter pylori (H.pylori) is a gram-negative bacterium that has infected more than half of the worlds population. This pathogen colonizes the human gastric mucosa and is usually acquired during childhood. It is an important cause of peptic ulcers, chronic gastritis and stomach cancer. Among the risk factors for acquisition of H. pylori infection, poor socioeconomic status, poor sanitization and hygiene practices, and contaminated food and water, are the most significant ones. The main route of H. pylori transmission is still unknown. Studies show that H.pylori bacteria can spread directly from one person to the other, or indirectly from an infected person to the environment. Person to person transmission is divided into fecal-oral, gastric-oral, oral-oral, sexual routes. Presently, interpersonal pathways are more acceptable than environmental exposure routes. Literatures indicate the presence and survival of H. pylori in food samples, such as milk, vegetables and meat, and suggest these foods may play an important role in the environmental transmission of this pathogen. In addition, other studies report the presence of H. pylori in the gastric tissue of some animals (e.g. sheep and cow) and therefore, it is likely they participate in the food chain transmission as reservoirs besides human. Although there are findings which indicate the probable role of food products in the environmental transmission of H. pylori, there is still not enough direct evidence to confirm this and more studies are needed. However, attention to food contamination sources (unhygienic water) and controlling them may prevent transmission of pathogens associated with health.

The Refugee and Immigration Crisis in Europe: Urgent Action to Protect the Mental Health of Children and Adolescents

We read with great interest the recent study by Stevens et al., which well documented the major indicators of emotional and behavioral problems among immigrant adolescents in different countries [1]. Stevens’s study and the accompanying editorial by Brenick and Titzmann [2] truly underline the fundamental threats to these immigrants’ physical and psychological health [1,2]. At the present moment, the refugee crisis is a critically important issue in Europe. The pastmonths have seen a rapid increase in the numbers of refugees that are entering Europe from theMiddle East (especially Syria) or are moving from Eastern to Western Europe over the Italian and French borders due towar and political conflicts in their home countries. These refugees, most accompanied by children, have come a long way in pursuit of the dream of better life in Europe. However, upon their arrival, they face many unexpected problems, such as registering for residency, finding housing, and adapting to new situations that may give rise to disappointment and hopelessness [3,4]. Refugee children bear much of the weight of these difficulties and limitations. Previous studies have revealed that the children of immigrants can face psychological problems arising from the feelings of estrangement and seclusion that can result from attempts to adapt to a new society and experiences [5,6]. It is well documented that the prevalence of severe mental health and behavioral problems among immigrant children is higher than among their native peers, and that they are at higher risk of experiencing multiple traumatic incidences [7,8]. Further, current reports regarding the mental health status of refugees in Europe indicate that the level of psychosocial damage among refugees is increasing due to difficult life conditions, lack of sufficient supportive services, and an uncertain future [3,4]. Together, this evidence suggests that mental problems among refugees and their children will continue to increase in the future. Is essential that policymakers in affected European countries make efforts to provide more caring and supportive facilities for refugees and immigrants. In order to improve the unfavorable mental health and educational conditions of these children and adolescents, they must be treated as minors, not immigrants.

Resistance of Helicobacter pylori to furazolidone and levofloxacin: A viewpoint

In their review, Arslan et al[1] did not describe the status of Helicobacter pylori (H. pylori) treatment with furazolidone and the resistance to this antibiotic. We have presented different surveys showing the resistance of H. pylori to furazolidone from Asia and South America. The resistance rates varied but were mostly low (< 5%). There are not enough data on its efficacy and resistance in the United States and Europe. H. pylori mutations occurring in the oorD gene, including A041G, A122G, C349A(G), A78G, A112G, A335G, C156T and C165T, and in the porD gene, including G353A, A356G, C357T, C347T, C347G and C346A, have been indicated to be possibly related to the observed resistance. Additionally, to complete Arslan et al’s statement regarding levofloxacin resistance, it should be noted that compound mutations of N87A, A88N and V65I at codon Asn-87 were recently observed in the gyrA gene for the first time. However, the results on these topics are not sufficient, and more worldwide studies are suggested.

Letter: levofloxacin resistance – a challenge for the treatment of Helicobacter pylori infection

SIRS, We read with great interest the systematic review and meta-analysis by Chen et al., reviewing the trend of efficacy of levofloxacin-based triple therapy (including a proton pump inhibitor (PPI), levofloxacin and amoxicillin) in the treatment of Helicobacter pylori worldwide since 2000–2016. The authors addressed most of the issues related to the topic of their article, however, we have some comments on their review. Chen et al.’s article did not mention a randomized trial by Molina-Infante (2008–2009), in which it was reported that triple regimen therapy (containing levofloxacin, amoxicillin and omeprazole), as the first-line treatment, had intention-to-treat and per-protocol cure rates of 80% and 82.6%, respectively. The authors declared that higher dosage of PPIs does not affect the eradication rate of levofloxacin-based triple therapy. This statement needs to be discussed. To our knowledge, efficacy of antibiotics in acidic environments is low and it increases using acid suppression drugs, such as PPIs. It has also been revealed that some patients are resistant to PPIs due to the rapid PPIs metabolism. Therefore, it would be better the authors considered this issue in their method and analysis, to give more precise results. But if we assume that the authors’ finding is acceptable, one of the appropriate suggestions can be substitution of PPIs by other drugs, such as H2 blockers, in the triple therapy regimen with levofloxacin. Chen et al. discussed the rate of primary resistance of levofloxacin against H. pylori in different countries as subgroup analyses – for example, Belgium, France and Japan. There are other studies such as Spain (14.5%, 2010), China (55.7%, 2007–2009), Ireland (11.7%, 2008–2009), Senegal (15%, 2007–2009), and Poland (5.85%, 2006–2012). A study by Phan et al. in Vietnam (2012–2014), showed a primary resistance rate of 35.6%, which was significantly higher in females (55.8%) than in males (28.6%). In addition, an investigation in South Korea indicated that the primary resistance rate to levofloxacin increased from 4.7% to 28.1% during 2003– 2012. Moreover, some studies showed that the rate of resistance increases with age. 9, 10 So far, no meta-analysis has been published assessing the exact rate of primary levofloxacin resistance and we suggest such study, especially considering the potential effect of age on the resistance. Also, because of the differences in the rate of levofloxacin resistance between countries, it is proposed that the treatment guidelines for H. pylori infection should be geographically designed.

Helicobacter pylori antibiotic resistance: Can herbal medicine be an alternative for the treatment?

Sir, We read with interest the article by Khademi et al., in which they well discussed the high antibiotic resistance rate of Helicobacter pylori, geographical variation in the resistance, and the molecular mechanisms of antibiotic resistance.[1] Prevalence of H. pylori infection is about 50% in the world. This pathogen is responsible for peptic ulcer disease, chronic gastritis, and gastric cancer. Unfortunately, the efficacy of the standard triple and quadruple therapy for eradication of H. pylori infection is seriously challenged because of the antimicrobial resistance problem.[2] Therefore, it is needed to choose new alternatives with high efficiency and less side effects. In this regard, medicinal herbs can be one of the desirable options due to their positive effects in the treatment of gastric ulcers.[3] During the last years, researchers have performed a number of experimental studies on various plants to evaluate their antiulcer and anti-H. pylori activities and to discover the bioactive compounds although most of them were done in vitro. For instance, it was revealed that flavonoids (especially, quercetin) have antisecretory, anti-inflammatory, antioxidant, and antihistaminic effects, and also, the role of these polyphenolic composites against H. pylori has been discussed.[4] Besides, other phenolic compounds such as quinones (cytoprotective) and phenolic glycosides (antisecretory) were reported as gastroprotective factors. Likewise, terpenoids as antiulcer compositions with cytoprotective activity enhance the production of mucus in the stomach. Furthermore, saponins have antisecretory mechanisms of action.[5] In addition to these, it is demonstrated that plants including Aloe vera, ginger, licorice, chamomile, and turmeric can have a significant effect on treatment of peptic ulcer disease through their cytoprotective and anti-H. pylori activities[4,5] Antibiotic resistance of H. pylori is presently a remarkable issue. According to the mentioned results, this hypothesis is considered that the antiulcer and gastroprotective properties of several medicinal herbs potentially have positive effects on treatment of H. pylori and its complication in humans. Therefore, it is proposed that more experimental and clinical studies be conducted on different medicinal plants to design new and effective natural drugs against H. pylori infection, considering the geographic and genotypic resistance patterns of this pathogen. Financial support and sponsorship Nil. Conflicts of interest The authors have no conflicts of interest.

Letter: global emergence of Helicobacter pylori antibiotic resistance - unanswered questions.

SIRS, We read with great interest the article by Thung et al., who discussed the important issue of Helicobacter pylori resistance to different antibiotics, and the alternative regimens to standard triple therapy (composed of a proton pump inhibitor, clarithromycin and amoxicillin/ metronidazole). However, this review did not clarify some essential issues. Thung et al. declared furazolidone as a potential alternative antibiotic, but they did not state its resistance against H. pylori. This is a considerable problem due to its negative effect on the eradication rate. Studies in Asia show different prevalences of furazolidone resistance between countries during the last years, for instance 16.8% in China, 13.8% in India and 21.6% in Iran. 3 Resistance to furazolidone is possibly related to six mutations in porD and oorD genes on the chromosome of this bacterium. However, more surveys are widely needed in this regard. The authors also debated about multidrug resistance of H. pylori to several antibiotics. Studies indicate that resistance to three or more antibiotics has been developed in about 15% of clinical isolates of this bacterium. One of the reasons for multidrug resistance can be explained by over expression of efflux pump gene hefA. In fact, this genetic mechanism can probably decrease the minimum inhibitory concentrations of different antibiotics (such as amoxicillin and tetracycline) against H. pylori strains and cause a reduction in the eradication rate. In order to find new evidence for this topic, continuous investigations are necessary. Increasing resistance to H. pylori infection has enhanced concerns about a decline in the efficiency of the same antibiotics in treatment of other diseases (e.g. regarding clarithromycin as the second-line treatment of multidrug resistance tuberculosis). In addition, studies indicate that the pattern of antibiotic resistance can regionally change within countries. Therefore, we believe that the antibiotic resistance patterns of H. pylori can be extensible to infection with other bacterial strains and affect their efficacy in treatment of infectious diseases in an area. There are no reports about this issue and it is proposed that such studies be performed at local scales.

Relationship between β-Thalassemia minor and Helicobacter pylori infection

Background: Until now, no study has been reported investigating the association between β-thalassemia minor and Helicobacter pylori (H. pylori) infection. This study was designed to compare H. pylori infection rate between β-thalassemia minor patients and healthy controls. Methods: A number of 100 β-thalassemia minor patients (50 males, 50 females) and 100 gender-matched healthy controls were prospectively recruited in this study in a period of 3 months. The study population consisted of the people who referred to a health center in Babol, North of Iran, for premarital counseling. H. pylori status was assessed by measuring the anti-H. pylori IgG antibodies using enzyme-linked immunosorbent assay. Demographic information and informed consent were collected from all participants. Results: The overall H. pylori infection rate was 43%. The infection was significantly more prevalent in thalassemia patients (53%) than in the controls (33%) in both univariate (OR=2.29, 95% CI: 1.3-4.06) and multivariable analyses (OR=2.05, 95% CI: 1.12-3.76). Age was the only significant factor which was positively correlated with the infection in β-thalassemia minor cases (OR=1.11, 95% CI: 1.02-1.2). Gender, blood groups, residency, and education level were not related to the infection. Conclusions: According to the results, it can be concluded that β-thalassemia minor patients are possibly more susceptible to H. pylori infection than healthy people. Further studies are needed to discover more about the exact mechanisms of increased susceptibility to H. pylori infection in β-thalassemia minor patients.

Editorial: the prevalence of Helicobacter pylori infection worldwide-knowns and unknowns. Authors' reply

all included countries, there was also considerable heterogeneity. The prevailing explanation is that this variability reflects real differences in the prevalence of the infection. However, as Zamani et al noted, our confidence in these results is undermined because of the variability in the sampling methods and diagnostic tests among studies. Furthermore, all the comparative analyses reported in this paper (between countries and continents; male/female; children/adults; older/recent studies) were between-study comparisons, which, understandably, are less reliable than within-study comparisons, which have not been conducted. Ideally, the risk of bias (methodological “quality”) of individual studies should have been assessed with a valid tool or a justified modification thereof, and subgroup analyses should have been performed for the (few) studies at low risk of bias vs studies at not-low risk of bias. When the certainty (“quality”) of the evidence is assessed by GRADE (Grading of Recommendations Assessment, Development and Evaluation), it is “very low,” meaning that further research is very likely to change existing estimates. Does this mean that we need yet another SRMA that addresses the above-mentioned issues? We do not think so. It is unlikely that such a project would produce much incremental knowledge. The overall conclusions would remain unchanged: large variability in the prevalence of H. pylori infection and very low certainty in the estimates. What is needed is further and better primary research with representative sampling, accurate diagnostic methods and high reporting standards that will provide accurate estimates of the prevalence of H. pylori infection in separate countries, including their regions and subpopulations. The evidence for eradicating H. pylori in the general population as a preventive strategy for gastric cancer is accumulating. However, the decision to implement such strategies will be taken by distinct national or regional governments only if accurate and reliable prevalence maps are available for their own jurisdiction. Ideally, such research efforts should also map the prevalence of H. pylori antibiotic resistance; such data are vital for the appropriate selection of eradication therapy, but currently are largely absent for most regions and countries.

Hematologic disorder: A manifestation of helicobacter pylori infection

Dear Editor, Colonization of H.pylori as a bacterial pathogen in the stomach can cause a number of gastric diseases, such as peptic ulcers, chronic gastritis and gastric cancer (1, 2). Over the past years, a series of systemic diseases has been reported to be potentially related to H. pylori infection, including cardiovascular, neurologic, hepatobiliary, dermatologic, endocrine and metabolic, immunologic, respiratory and urogenital diseases (3-6). Hematologic disorders were other extragastric manifestations of H. pylori. Several studies presented that H. pylori can be a causative factor for anemia, iron deficiency and iron deficiency anemia (IDA) (3, 7, 8). In addition, it was stated that eradication of this pathogen not only led to increase in response to oral iron therapy and level of ferritin, but also could cure anemia completely in several cases with unexplained IDA (5, 8, 9). Idiopathic thrombocytopenic purpura (ITP) is the other hematologic disease shown to be related to infection of H. pylori. It was reported that treatment of the infection was associated with increased platelet count in some patients with ITP. Modulation of Fcγreceptor balance of monocytes or macrophages, and mimicry of platelet antigens by H. pylori peptides are putative mechanisms explaining the relation between ITP and this infection (9). It was also proposed that H. pylori-induced gastritis could be a leading factor of vitamin B12 deficiency in patients (10). Altogether, ITP is considered as an accepted hematologic manifestation of H. pylori infection. Besides, it seems that the infection can possibly decrease level of iron storage, resulting in IDA. Therefore, H. pylori treatment can be indicated in patients with IDA, ITP and vitamin B12 deficiency.