Pathogenic diversity of Helicobacter pylori

Helicobacter pylori has been shown to possess a very heterogeneous genoma despite its common phenotypic properties. Some characteristics relevant to pathogenesis have also been found to be heterogeneous. This is the case for adherence properties and the amount of urease produced, but it was not possible to relate these properties to disease entities. A vacuolating cytotoxin which alters epithelial cells has been found in about 60% of strains isolated from patients with ulcers versus 30% from those with gastritis only. The cagA gene can be used as a marker to detect the cag pathogenicity island. This DNA fragment seems to induce an increased inflammation in the gastric tissue via release of interleukin 8 by the epithelial cells. The association of this marker is strongly linked with ulcers compared with gastritis only (80% vs 55%, respectively). A number of other properties may be heterogeneous, but the low number of strains studied does not allow conclusions to be drawn.     

Expanding allelic diversity of Helicobacter pylori vacA

The diversity of the gene encoding the vacuolating cytotoxin (vacA) of Helicobacter pylori was analyzed in 98 isolates obtained from different geographic locations. The studies focused on variation in the previously defined s and m regions of vacA, as determined by PCR and direct sequencing. Phylogenetic analysis revealed the existence of four distinct types of s-region alleles: aside from the previously described s1a, s1b, and s2 allelic types, a novel subtype, designated s1c, was found. Subtype s1c was observed exclusively in isolates from East Asia and appears to be the major s1 allele in that part of the world. Three different allelic forms (m1, m2a, and m2b) were detected in the m region. On the basis of sequence alignments, universal PCR primers that allow effective amplification of the s and m regions from H. pylori isolates from all over the world were defined. Amplimers were subsequently analyzed by reverse hybridization onto a line probe assay (LiPA) that allows the simultaneous and highly specific hybridization of the different vacA s- and m-region alleles and tests for the presence of the cytotoxin-associated gene (cagA). This PCR-LiPA method permits rapid analysis of the vacA and cagA status of H. pylori strains for clinical and epidemiological studies and will facilitate identification of any further variations.     

Virulence-associated genes as markers of strain diversity in Helicobacter pylori infection

To establish a marker of strain diversity of Helicobacter pylori, a genetic examination was performed based on the detection rates by PCR of cagA and vacA, which are known to be virulence-associated genes. The test strains were obtained from 70 patients suffering from gastric ulcer (GU), 82 patients with duodenal ulcer (DU) and 48 patients with gastritis (GS). Fragments located in the three different regions of vacA were amplified; V1 being the upstream portion, V2 the mid-portion and V3 the downstream portion. For cagA, the detection rates were 70% for GU, 79% for DU and 50% for GS, showing a significantly higher rate for DU than for GS (P = 0.0005). With V1, the detection rates were 90% for GU, 90% for DU and 69% for GS, giving a significantly higher rate for GU than for GS (P = 0.0036) and also giving a significantly higher rate for DU than for GS (P = 0.0019). With V2, the detection rates were 60% for GU, 70% for DU and 44% for GS, giving a significantly higher rate for DU than for GS (P = 0.0024). The differences in vacA gene polymorphism were closely related to the evidence of gastroduodenal ulcers in H. pylori infection. Furthermore, the detection rates of cagA and polymorphisms of vacA by PCR could be used as markers of strain diversity in H. pylori-induced gastroduodenal ulcer.     

Isolation of a genetic locus associated with metronidazole resistance in Helicobacter pylori

We examined the molecular mechanism of metronidazole resistance by constructing a lambda-Zap II phagemid expression library with genomic DNA from a metronidazole-resistance strain of Helicobacter pylori. Twenty-two clones were found to have elevated MTZ resistances in XLOLR strain of E. coli. Phagemids belonging to the twenty two clones were extracted and then retransformed into the XLOLR strain of E. coli. After MTZ selection, five clones could confer metronidazole resistance consistently. According to Southern hybridization and DNA sequencing, the five clones contained a same locus, recA. In addition, transforming the five clones into BL21 strain of E. coli produced a higher resistance to MTZ. Interestingly, electroporation of one of the five phagemid clones into two MTZ sensitive H. pylori yielded MTZ resistant strains. Comparing amino acid sequence in MTZ resistant with sensitive isolates revealed two point mutations at this locus. Above results suggest that mutation in recA may be associated with metronidazole resistance of H. pylori.     

Helicobacter pylori infection and genetic polymorphisms for cancer-related genes in gastric carcinogenesis

The development of gastric cancer is a multistep process that is multi-factorial. An association with the Helicobacter pylori infections, gastric atrophy and gastric cancer has received recent attention. The objective of this study was to elucidate the risk factors for gastric cancer by using molecular epidemiological techniques for genetic susceptibility, gastric atrophy and serum markers including H pylori infection. We used an age- and gender-matched case-control study, where patients with benign gastric lesions were the controls. Low serum pepsinogen I levels (cut-off < 50 ng/mL) and low pepsinogen I/pepsinogen II ratios (cut-off < 3.0) were significantly associated with the risk of gastric cancer (odds ratio [OR] = 3.53: 95% confidence interval [CI] = 2.46-5.09 and OR = 4.73: 3.26-6.88, respectively). However, seropositivity of serum immunoglobulin G (IgG) antibody against H pylori (OR = 1.09: 0.74-1.61) was not associated with gastric cancer, even when analyzed by age greater than or less then 50 years. Specific genotypes of the cytochrome p450 2E1 (CYP2E1) RsaI polymorphism and glutathione-S-transferase (GST) M1 gene deletion were determined but were not associated with gastric cancer; however, a Lmyc genetic polymorphism was associated with gastric cancer (OR = 1.55: 1.03-2.34). Therefore, in this Japanese study, atrophic mucosal change, indicated by serum pepsinogen levels, is a possible risk factor for gastric cancer.     

Distribution of genetic diversity in relation to chromosomal inversions in the malaria mosquito Anopheles gambiae

The epidemiology of malaria in Africa is complicated by the fact that its principal vector, the mosquito Anopheles gambiae, constitutes a complex of six sibling species. Each species is characterized by a unique array of paracentric inversions, as deduced by karyotypic analysis. In addition, most of the species carry a number of polymorphic inversions. In order to develop an understanding of the evolutionary histories of different parts of the genome, we compared the genetic variation of areas inside and outside inversions in two distinct inversion karyotypes of A. gambiae. Thirty-five cDNA clones were mapped on the five arms of the A. gambiae chromosomes with divisional probes. Sixteen of these clones, localized both inside and outside inversions of chromosome 2, were used as probes in order to determine the nucleotide diversity of different parts of the genome in the two inversion karyotypes. We observed that the sequence diversity inside the inversion is more than three-fold lower than in areas outside the inversion and that the degree of divergence increases gradually at loci at increasing distance from the inversion. To interpret the data we present a selectionist and a stochastic model, both of which point to a relatively recent origin of the studied inversion and may suggest differences between the evolutionary history of inversions in Anopheles and Drosophila species.     

Helicobacter pylori in children

Helicobacter pylori is the major cause of antral gastritis in children, however, it is not always associated with symptoms. The exception to this occurs in duodenal ulcer disease with which H. pylori is linked in children albeit less strongly than in adults. Duodenal ulcers do not recur in older children following eradication of H. pylori. The importance of asymptomatic carriage of H. pylori in children, particularly in relation to the duration of this infection and the subsequent development of gastric cancer, remain to be established. Helicobacter pylori is associated with both hypochlorhydria and persistent diarrhoea in children in developing countries, but the significance of this association is still unknown. Although there is no consensus on the optimal regimen for treating H. pylori infection in children, dual therapy with amoxycillin and bismuth subcitrate for 2 weeks followed by monotherapy with bismuth subcitrate for a further 6 weeks will eradicate H. pylori infection in the majority of children. Those who relapse may be treated with a repeat course plus metronidazole for 4 weeks. Compliance with such regimens is a problem and shorter treatment courses that are equally effective in children need to be defined. Similarly, studies are required on the influence of the intrafamilial reservoir of H. pylori infection on relapse after treatment and the need for whole family eradication therapy.     

Helicobacter pylori in 1997

In this review Helicobacter pylori (H. pylori) infection and its relation to different diseases is presented. H. pylori doesn't cause inconvenience to most infected people, though all infected persons have chronic active gastritis. The 10 year risk of peptic ulcer for people infected with H. pylori is about 10%. Randomized double-blinded trials have shown that eradication of H. pylori can cure most patients with peptic ulcer disease. Some people infected with H. pylori develop atrophic gastritis which is a risk factor for development of gastric cancer. It is not known if H. pylori screening and eradication would have a prophylactic effect against gastric cancer. It is also unknown if persons with non-organic dyspepsia and persons in long-term treatment with proton-pump-inhibitors would benefit from H. pylori eradication.     

Prevalence of Helicobacter pylori resistance to several antimicrobial agents in a region of Germany

To evaluate the prevalence of resistance among Helicobacter pylori in Germany, the minimum inhibitory concentrations of amoxicillin, tetracycline, clarithromycin, and metronidazole were determined by means of the E test, for 271 Helicobacter pylori isolates cultured from biopsies taken during routine endoscopies in 1996 and 1997. The prevalence of metronidazole resistance was 32.1%, with resistance found more frequently in women (38.5%) than in men (24.4%). Clarithromycin resistance was rare (3.3%). Eight of nine strains resistant to clarithromycin were also resistant to metronidazole. Resistance to either metronidazole or clarithromycin was significantly (P=0.022) higher in patients with duodenal ulcer. No strain was found to be resistant to amoxicillin or tetracycline.     

Helicobacter pylori in South America

Interviews of a representative sample of 201 physicians (general practitioners, gynecologists, pediatricians) with a mean age of 47 years show: there is a unmanageable amount of information about drugs and their risks. The physicians prefer practical experience rather than specialized literature. As a result they plead for a central authority of information with periodical reports on the current knowledge of drug-therapy and with the possibility of therapeutical consultation.     

Helicobacter pylori infection in children

BACKGROUND: Although immigrants to the United States are usually ethnic minorities and socioeconomically disadvantaged, foreign-born women generally have lower rates of low birth weight infants than do US-born women. OBJECTIVE: To measure the relationship between maternal birthplace, ethnicity, and low birth weight infants. DESIGN: Retrospective cohort study of birth certificate data. SETTING: California, 1992. SUBJECTS: Singleton infants (n = 497 868) born to Asian, black, Latina, and white women. MAIN OUTCOME MEASURES: Very low birth weight (500-1499 g), moderately low birth weight (1500-2499 g), and normal birth weight (2500-4000 g, reference category). RESULTS: Foreign-born Latina women generally had less favorable maternal characteristics than US-born Latinas, yet foreign-born Latina women were less likely to have moderately low birth weight infants (odds ratio, 0.91; 95% confidence interval, 0.86-0.96) than US-born Latinas after adjusting for maternal age, education, marital status, parity, tobacco use, use of prenatal care, and gestational age. While foreign-born Asian women generally had a less favorable profile of maternal characteristics than US-born Asians, there was no statistically significant difference in the odds of very low birth weight or moderately low birth weight infants between foreign- and US-born Asian women. Foreign-born black women had more favorable maternal characteristics than US-born women, but there was no significant nativity difference in very low birth weight or moderately low birth weight between foreign- and US-born black women after adjusting for maternal and infant factors. CONCLUSIONS: The relationship between maternal birthplace and low birth weight varies by ethnicity. Further study is needed to understand the favorable pregnancy outcomes of foreign-born Latina women.     

Treatment of Helicobacter pylori infection

The article presents information gained from a survey among Norwegian hospitals in March 1997 concerning their treatment of infections with Helicobacter pylori. Altogether 52 hospitals answered the questionnaire. A combination of proton pump inhibitors, metronidazole and clarithromycin was used by 59% as first choice and urea quick test (94%) and urea breath test (42%) as the primary diagnostic procedures, whereas serology was in little use (17%). Besides ordinary ulcer disease, indications for treatment were: ulcer induced by non-steroid anti-inflammatory drugs (79%), gastrooesophageal reflux (37%), non-ulcer dyspepsia (14%) and cancer prophylaxis (14%). The gastro group at the Department of Pharmacotherapeutics at the University of Oslo invited specialists from all health regions to discuss indications for treatment of H pylori, the diagnosis and the role of general practitioners. The extensive use of clarithromycin might be doubtful due to development of resistance. Indications for treatment of H pylori other than ulcer disease and mucosa associated lymphoid tissue lymphoma are still uncertain. Uncritical use of serological tests in primary care should be discouraged. At present there is no uniform strategy for the diagnosis and treatment of H pylori infection, and a coordinated strategy between general practitioners and specialists is needed.     

The microbiology of Helicobacter pylori

In this case the authors describe a patient with primary microinvasive adenocarcinoma of the eso-cervix, with the cervical canal not involved by the pathology, diagnosed by colposcopy followed by biopsy. Before the diagnosis of microinvasive adenocarcinoma the patient was scheduled for electrocautery of the suspicious area due to the fact that previous Pap-smears had always been negative. The authors underline the important role of colposcopy as a diagnostic tool that should be mandatory before any surgical therapy on the cervix and that allowed to diagnose such a rare cervical tumor.     

Physiopathology of Helicobacter pylori infection

The gastric juice of Helicobacter pylori-infected individuals contains substantially higher levels of phospholipase A2 (PLA2) than that of individuals who are not infected. We present a new theory for how this H. pylori-induced PLA2 activity in gastric juice may play a major role in the development of peptic ulcer disease. When activated at neutral pH (pH 6.5-7.0), PLA2 may damage the surfactant-like, phospholipid-rich layer which constitutes an important part of the mucus barrier. Pepsin and other proteases, activated at low pH (pH 1.0-3.5), may then denature and cleave PLA2-exposed proteins. Peptic ulcers therefore tend to develop in regions exposed to changing luminal pH, such as the duodenal bulb when acid production is high or normal, or in the stomach when acid secretion is low.     

Helicobacter pylori gastric infections in children

OBJECTIVES: Numerous reports have established the association of Helicobacter pylori and recurrent abdominal pain in children. We investigated the clinical, bacteriological and therapeutic features of our patients seen over a 1 year period. METHODS: We investigated 121 children during 1992 in Hospital Saint Vincent-de-Paul, Paris. At endoscopy, biopsies were taken and sent for histology and bacteriology and urease testing. A decision regarding treatment by amoxicillin and metronidazol was made after positive results of bacteriology and/or histology. RESULTS: Heliobacter pylori was found in 47 antral biopsies after pathology examination with Giemsa staining alone 16 times, bacterial culture 9 times and both methods 22 times. Abdominal pain was the prominent symptom, occurring in 35.5% of Helicobacter pylori+patients. In 25 of the positive negative patients, a nodular gastritis was observed (53.1%) and in 27.6% of them a weight loss or a delay in weight gain. Few patients became after combined treatment with amoxicillin and metronidazol whereas eradication rates after triple therapy with amoxicillin-metronidazol and H2 antagonist or proton pump blocker were higher. CONCLUSION: Helicobacter pylori related gastritis is a common cause of abdominal complaints in children. The most common symptom is recurrent abdominal pain. Antral nodularity is a peculiar endoscopic finding in children. Two-drug therapy associating amoxicillin-metronidazol is often ineffective to eradicate the bacteria whereas eradication rates after triple therapy amoxicillin-metronidazol and H2 antagonist or proton pump blocker are higher.     

Treatment of Helicobacter pylori infection

Since acceptance of the association between Helicobacter pylori and peptic ulcer disease, eradication of H. pylori has become the standard of care in the treatment of peptic ulcer disease. Unfortunately, eradication therapy is no easy task, especially when one is faced with a myriad of drug combinations with varying degrees of efficacy and tolerability. The following is a review of the literature regarding the drugs and drug combinations used to eradicate H. pylori and their effectiveness both as single agents and in combination.     

Helicobacter pylori infection in congestive gastropathy

This report describes a family who demonstrated anomalies of tooth form and eruption of the lower second premolar. Observation of the second premolars remaining in the mother's and father's dentitions included ectopic eruption with impaction and substantial spacing between the first and second premolars. Four siblings were also examined--three boys aged 15, 14 and 12 years, and one girl aged 11 years. Anomalies of the second premolar recorded in the males and female include: congenital absence, ectopic eruption with impaction, delayed eruption and spacing. Associated anomalies included: congenital absence of other permanent teeth and spacing. It appears that the defect in tooth form and eruption is of a genetic origin, affecting both males and females. The condition(s) did not appear to be associated with a syndrome and the human papilloma virus lesions noted in all family members were not considered to be related to the dental defects. This family demonstrated two anomalies of the lower second premolar: congenital absence and disturbance in tooth eruption. The question raised by this case report is whether these two anomalies are inherited as separate traits or whether failure of tooth eruption is a variation in expression of the same genetic factor that results in oligodontia.