Over three decades have passed since the discovery of Helicobacter pylori (H. pylori), and yet many questions about its treatment remain unanswered. For example, there is no certainty regarding continued use of current antibiotic therapy against H. pylori. The bad news is that even combined regimens are also unable to eradicate bacterial colonization. The worst problem with H. pylori chemotherapy is that even if we identify the most successful regimen, it cannot eliminate the risk of re-infection. This problem is further complicated by the fact that clinicians have no information as to whether probiotics are useful or not. Moreover, to date, we have no large scale produced vaccine effective against H. pylori. Due to the relatively rapid and abundant dissemination of guidelines globally reported concerning management of gastric cancer prevention and therapeutic regimens, clinicians may choose a vaccine as better effective weapon against H. pylori. Therefore, a radical shift in adopted strategies is needed to guide ultimate decisions regarding H. pylori management. In light of failures in vaccine projects, we should identify better vaccine design targeting conserved/essential genes. The unique character and persistence of H. pylori pose obstacles to making an effective vaccine. Preferably, in developing countries, the best reasonable and logical approach is to recommend prophylactic H. pylori vaccine among children as an obligatory national program to limit primary colonization. Trying to produce a therapeutic vaccine would be postponed until later. In reality, we should not forget to prescribe narrow spectrum antibiotics. In the current review, I draw a route to define the best adopted strategy against this rogue bacterium.

Detection of Helicobacter pylori after triple therapy is usually carried out by either rapid urease test (RUT), urea breath test (UBT), histology, bacterial isolation, and single round PCR or serological tests. In this study, antral biopsy specimens from 25 patients were tested for H. pylori by RUT, culture, histology, and nested PCR in their antral biopsy specimens before and after treatment. Three genes, namely, heat shock protein (hsp60), phosphoglucosamine mutase (ureC), and flagellar export ATP synthase (fliI) of H. pylori were targeted. Of the 25 antral biopsy specimens, the RUT, culture, histology, and nested PCR positivity dropped from 81.8% to 12%, 31% to 0%, 100 to 84%, and 100% to 92%, respectively, before and after therapy. Further, hsp60 specific amplicons from 23 out of 25 patients gave identical restriction pattern, while 6 fliI and 1 ureC specific amplicon produced different restriction pattern. Furthermore, variations in fliI gene sequences in H. pylori after treatment were also confirmed by sequencing and compared in silico. Nested PCR based detection of H. pylori is more sensitive method to detect H. pylori after therapy than culture, RUT, and histology. Further, this study suggests that H. pylori is not eradicated completely after triple therapy.

The incidence of 'true' re-infection with Helicobacter pylori after successful eradication remains uncertain.

To determine the worldwide rates, risk factors and clinical implications of 'true' re-infection of Helicobacter pylori. 'True' re-infection of H. pylori is defined as the situation where tests for H. pylori infection, which were negative for 12 months after eradication, become positive again at a later stage.

Thirty six studies were identified through a literature search to be able to produce annual rates of 'true' re-infection, and data from 33 original articles were considered reliable and adequate in the further review. Generally, the reported rates varied from 0% to 23.4% in adults and from 1.9% to 9.6% in children. Most studies from developed countries reported rates of less than 1%, whereas relatively higher rates were reported in most of the developing countries. Small sample sizes included in the studies appeared to be associated with increased re-infection rates. Interfamilial transmission is the major cause of re-infection, although iatrogenic re-infection through contaminated endoscopic equipment has been reported.

Helicobacter pylori re-infection is not a concern in a clinical setting, especially in the developed world; however, caution must be exercised in most developing countries.

Helicobacter pylori is one of the most commonly encountered human pathogens. It has been shown to be closely associated with peptic ulcer disease (PUD), gastric adenocarcinoma, and the gastric mucosa-associated lymphoid tissue (MALT) that may lead to gastric lymphoma. The current diagnostic methods include histology, microbiological culture, classic serology, urease activity detection, polymerase chain reaction (PCR) and stool antigen detection. Its treatment modality options are multiple; however, a triple regimen consisting of a proton pump inhibitor (PPI), and two antibiotics for 10 to 14 days is preferred. Drug resistance is a growing problem in this organism and new therapeutic options are currently limited.

An association of H. pylori infection with chronic gastritis, peptic ulceration and gastric cancer is known.

Prevalence of IgG antibodies to Helicobacter pylori in children in the Bloemfontein, South Africa area was studied. Children attending the general pediatric outpatient department at Pelonomi Hospital in Bloemfontein were grouped according to age. A minimum of 100 children was investigated in each age group. Baseline demographic and socioeconomic data were collected.

The study showed a high prevalence of H. pylori antibodies. Prevalence increased with age: 13.5% in children 3 months-2 years, 48.5% at 2-5 years, 67.3% at 5-10 years and 84.2% at 10-15 years. Investigation of the socioeconomic data in relation to the prevalence of H. pylori was inconclusive.

This high prevalence needs further study.

The cagA gene has been detected by PCR and DNA hybridization in 45 Helicobacter pylori strains isolated from children. For each child, clinical symptoms, endoscopic aspect of the gastric mucosa, and histological gastritis were evaluated. Gene-positive strains were associated with hemorrhagic gastritis in 66.6% of the children, while gene-negative strains were associated with hemorrhagic gastritis in 11.2% of the children (P = 0.0001). In addition, 88.8% of gene-positive strains were associated with severe histological gastritis (scores of 3 and 4), and gene-negative strains were collected from the gastric mucosa with the same type of infiltration of neutrophils and lymphocytes in the lamina propia in 55.5% of the children. These differences were statistically significant (P = 0.017). Gene-positive strains were also isolated more frequently from children with vomiting (P = 0.04), while the absence of clinical signs was not significantly different in cagA gene-positive or -negative patients. All of these observations confirmed the role of this cagA gene as a marker of gastric inflammation in children. The detection of this gene might be helpful to determine the degree of inflammation of the gastric mucosa in the absence of abdominal symptoms. We might better understand the natural history of H. pylori infection if we studied the evolution of gastritis in children with regard to the cagA status of isolated strains.

Helicobacter pylori is an important cause of chronic active gastritis and is strongly associated with peptic ulcer disease and gastric cancer. H. pylori colonizes the surface of the gastric epithelium with production of a number of factors, resulting in inflammation and an altered mucosa. H. pylori infection occurs world-wide and the mode of transmission most likely is from human to human via the fecal-oral and/or the oral-oral route. Treatment and, in the future, prevention of this infection may result in a marked diminution of upper gastrointestinal tract disease.

Helicobacter pylori is present in the antral region of the stomach in a majority of patients with gastritis type B. The specific mechanism whereby the organism participates in the development of disease remains uncertain. Since the organism is not invasive, we postulate that H. pylori produces a chemoattractant that recruits inflammatory cells to the antral region of the stomach. H. pylori was grown under microaerophilic conditions at 37 degrees C for 72 hr in Brucella broth containing 1% fetal bovine serum. Culture supernates were harvested after removal of organisms by centrifugation and filtration. The putative chemoattractant in culture supernates as well as that which might be present endogenously in the growth medium (negative control) was assayed against human neutrophils (PMN) in modified Boyden blind-well chambers using 3.0-microns membranes. We found that H. pylori supernates are chemotactic and showed up to 130% activity when compared to the positive chemoattractant control (zymosan-activated serum, a source of C5a). Minimal activity was observed with virgin growth medium. The chemoattractant activity is proportional to the number of colony forming units (CFU) of H. pylori. Preliminary characterization of the activity shows that the chemoattractant is stable in a boiling water bath for 15 min, activity is lost within 1 hr in acid or alkali, and the chemotactic factor has an approximate molecular weight of 8500 daltons. The factor has no amino-sugar and is negative for the lipid A portion of lipopolysaccharide.(ABSTRACT TRUNCATED AT 250 WORDS)

A total of 61 human gastric isolates of Helicobacter pylori were studied for their ability to induce an oxidative burst in human neutrophils measured by luminol enhanced chemiluminescence. About one third of the strains induced strong and rapid chemiluminescence in neutrophils even without serum opsonins and agglutinated these cells on glass slides within two minutes. For other strains complement was required, although even then the reactions remained at a lower level. The activating and agglutinating property was bound to the cells, heat labile, and sensitive to several enzymes but resistant to acid. Strains possessing such activity were more common in patients with peptic ulcer disease than in patients with active chronic gastritis only (p = 0.0261, Fisher's exact test, two tailed). The activity shown might be a new indicator for ulcerogenic strains and could also partly explain the accumulation of neutrophils in the gastric mucosa during H pylori infection.

The systemic immune response to Helicobacter pylori was studied in 247 infected adult patients before antimicrobial therapy and at different intervals following therapy. Endoscopy with simultaneous collection of biopsies was performed in all patients immediately before treatment, 4 to 6 weeks after the end of therapy and 6 to 12 months later. A 14C-urea breath test was performed 3 to 6 months after the end of treatment. Biopsy specimens were cultured and examined histologically using Giemsa stain. Sera were tested for Helicobacter pylori IgG antibodies with a commercial enzyme immunoassay using species-specific antigens. Overall, Helicobacter pylori was eradicated in 120 patients while the other 127 remained infected with the organism. The follow-up period ranged from 4 weeks to 33 months (mean 10.2 months). Pretreatment IgG levels did not differ significantly between the two groups of patients. Six weeks after the end of treatment a slight but definite decrease in the IgG antibody levels was seen irrespective of treatment success. In the 127 patients who remained Helicobacter pylori-positive, the level of IgG antibodies remained stable or increased with time. A continuous fall in antibody levels was observed following bacterial eradication in the other 120 patients, but the difference in antibody levels between treatment responders and nonresponders became significant only more than six months after the end of treatment (p = 0.001). Serological testing may be useful for monitoring the outcome of long-term treatment of Helicobacter pylori infection and obviate the need for endoscopy.

A membrane-associated 120 kDa protein of Helicobacter pylori with known species-specificity was isolated and used in an enzyme immunoassay (EIA) for the detection of Helicobacter pylori-specific IgG antibodies in patient sera. The EIA was compared with two other methods used for serodiagnosis of Helicobacter pylori infections: an EIA using sonicated whole Helicobacter pylori cell antigen and Western immunoblot. In a prospective study 127 unselected patients (76 patients with antrum gastritis, 51 patients without gastritis) who underwent gastroscopy were studied histologically and serologically. The EIA using the purified 120 kDa protein had the highest specificity (92%) compared with the EIA using a whole cell sonicate of a single Helicobacter pylori strain as antigen (60.7%) and the immunoblot (90.2%). The sensitivity was 96%, 100% and 92%, respectively. Sera of three control patients reacted strongly in all three methods, indicating possible Helicobacter pylori infection with negative histological findings. The EIA using the 120 kDa protein as antigen was shown to be a specific and sensitive technique for the serodiagnosis of Helicobacter pylori infections.

The prevalence of Helicobacter pylori infection in Zaire was determined by means of a [14C] urea breath test in 133 asymptomatic subjects, by culture and histological examination of biopsies in 324 consecutive endoscopy patients with chronic epigastric complaints, and by both the breath test and culture/histology in a subset of 92 patients. Sixty healthy Belgian students or hospital laboratory workers were also included for comparison. The prevalence of Helicobacter pylori was significantly higher in asymptomatic Zairian subjects (77.4%) than in the Belgians (30%; p less than 10(-6)). Infection was also acquired much earlier in life in Africans, 66% of the children aged 5 to 9 years already being infected versus none of the Belgian subjects below the age of 20 years. In Zaire, however, the prevalence of Helicobacter pylori in patients with gastroduodenal disorders (87.5%) was similar to that in the group of asymptomatic subjects (77.5%) after adjustment for age and other epidemiological parameters (gender, place of residency, education level, smoking and drinking habits) in a multivariate analysis. The high rate of acquisition of Helicobacter pylori infection in Zaire emphasizes the need to consider the baseline prevalence of Helicobacter pylori in a defined population when studying its association with various diseases.

A non-invasive serological assay devised in this laboratory had a sensitivity and specificity of 100% as determined by culture and confirmed by histology in a group of 47 patients who had undergone endoscopy. The correlation between serology and the non-invasive [14C] breath test was very good. Only one of 24 culture positive patients was, while all 23 culture negative patients were, breath test negative. In a group of 46 healthy elderly persons, however, significant anomalies between serology and breath test were observed. Only 83% of the breath test negative persons were seronegative, while only 68% of the breath test positive persons were seropositive. These results can be explained in terms of age related atrophic gastritis and immune incompetence, causing reduced colonisation and decreased antibody production, respectively. These investigations suggest that non-invasive tests for H pylori infection may not be reliable in the elderly.

The relationship between different features of gastric mucosal inflammation, intragastric pH and serum gastrin concentration and the distribution and quantity of Helicobacter pylori was studied in a series of 107 dyspepsia patients. H. pylori was identified in 62 cases (59%), and its presence was associated with increased amounts of mononuclear inflammatory cells and neutrophilic and eosinophilic leucocytes in both the antrum and the corpus. The number of H. pylori in the antral mucosa was significantly associated with the quantity of mononuclear inflammatory cells. It was also associated with glandular atrophy in antral mucosa, so that slight and moderate glandular atrophy were significantly more common in cases with abundant H. pylori. Intragastric pH and serum gastrin concentration were inversely related to the number of H. pylori in both the antral and corpus mucosa. H. pylori positive patients were also divided into groups according to proportions of H. pylori in the antral and corpus mucosa. In 5 of these patients (8%) the bacteria were present only in the corpus, and this group had a significantly more pronounced degree of glandular atrophy in the corpus mucosa, higher intragastric pH and a higher serum gastrin concentration than the other H. pylori positive patients. The other patients with a higher corpus H. pylori than antral H. pylori score (n = 25; 34%) also had a significantly higher intragastric pH and serum gastrin concentration than those with a corpus H. pylori score lower than or equal to the antral score, while the latter had more severe inflammation in the antral mucosa and a lower intragastric pH and serum gastrin concentration. The results suggest that inflammation in the antrum forms a favourable environment for H. pylori, while atrophy of the corpus glands, being connected with increased pH, leads to a diminished amount of H. pylori. They thus support the view that proliferation of H. pylori is dependent on acid produced by the corpus mucosa.

Sera from 100 children (ages, 6 to 16 years) presenting with upper gastrointestinal symptoms were examined for antibodies to Helicobacter pylori by enzyme-linked immunosorbent assay (ELISA) based on crude, loosely cell-associated antigens and a partially purified urease antigen preparation. All children underwent endoscopy, and 20 children were shown to have H. pylori infection by histology or direct culture. Serum anti-H. pylori immunoglobulin G (IgG) levels (crude antigen) were clearly raised in the infected group, particularly after preabsorption of sera against a Campylobacter jejuni antigen preparation, while IgM and IgA ELISA determinations did not discriminate between infected and H. pylori-negative patients. Only 14 children in the infected group had raised anti-urease IgG levels. Two patients in whom the organism was not demonstrated or cultured had raised specific IgG levels against both crude and urease antigens and pathological features consistent with H. pylori disease. Immunoblotting studies did not reveal any single protein antigen or simple combination of antigens that could be considered as a candidate for a more defined serodiagnostic reagent. Anti-H. pylori antibody determinations (crude antigen) performed on posttreatment samples from children in whom the organism could no longer be demonstrated suggested that sustained IgG levels may not be a reliable index of treatment failure. An IgG ELISA based on crude, loosely cell-associated antigens of H. pylori can be used for the serodiagnosis of H. pylori infection in childhood.

In a previous study, the recurrence of the Campylobacter pylori infection after apparently successful antibacterial therapy was determined to be due to recrudescence rather than reinfection. Although the DNA patterns of pre- and posttreatment isolates were very similar, we detected minor differences between the two patterns in about one third of the patients. These differences were not artifacts, but originated in the coexistence in the stomach of (sub)populations of bacteria with slightly different chromosomal DNAs, plasmids, or both. The presence of such (sub)populations was probably caused by mutation in vivo, as mutation in vitro was demonstrated in one patient after the original isolate was subcultured 10 times. Minor differences were not correlated with a difference in susceptibility to the antibiotic(s) that was used. An additional conclusion of this investigation was that the results of plasmid analysis should be interpreted very carefully when this method is used as an epidemiologic marker in the investigation of C. pylori infections.

Campylobacter pylori isolates from 37 symptomatic patients and 3 asymptomatic volunteers were examined by chromosomal DNA restriction endonuclease analysis and determination of plasmid profile. Restriction digests with HindIII, HaeIII, PvuII, and BglII produced clear and reproducible results that permitted discrimination between different strains. Only 35% of C. pylori isolates were found to have plasmid DNA. Isolates from different patients, including those from two pairs of siblings, had unique restriction patterns and plasmid profiles. Consecutive isolates obtained 1 year apart from each of two asymptomatic volunteers had identical restriction patterns and plasmid profiles, suggesting persistence of the same strain. A pair of isolates obtained one year apart from the third volunteer differed in plasmid DNA content but had similar chromosomal DNA restriction patterns. Plasmid profile determination and bacterial DNA restriction endonuclease analysis provide a reliable means of discriminating between different strains of C. pylori and may be useful for typing these organisms in epidemiologic studies.

Campylobacter pylori infection was sought in 382 consecutive patients referred for upper gastrointestinal endoscopy. Five antral biopsy specimens were taken from each patient: one was inserted into a CLO-test to detect the urease activity of C pylori, two were sent for histological analysis where multiple sections were stained by the Warthin-Starry silver method, and two were sent for microbiological evaluation by Gram stain and culture. A patient was deemed to be infected when C pylori was cultured or seen in either the histological sections or the Gram stain of the biopsy smear. One hundred and seventy four (46%) patients were infected. Culture, Gram stain, histological examination and the CLO-test showed sensitivities of 92%, 87%, 93% and 90%, respectively. In 27 (15%) infected patients an uneven distribution of C pylori was seen between samples in the biopsy pair sent for histology. Examination of multiple sections stained with Warthin-Starry silver was more sensitive at detecting infection (93%) than examination of multiple sections from only one biopsy specimen (84%). Fifty seven of 80 patients, biopsied a median seven days (range 5 to 55) after completing colloidal bismuth subcitrate treatment, were still infected with C pylori. There was no decrease in the sensitivities of the above tests to detect infection after treatment. It is concluded that at least two antral biopsy specimens should be examined when attempting to diagnose C pylori infection by histological methods.

Campylobacter pylori has been associated with gastritis, duodenal ulcer, gastric ulcer, and nonulcer dyspepsia. Evidence that C. pylori may be the causative agent or at least a major contributory factor in peptic ulcer disease has generated intense interest in the development of reliable methods for detecting C. pylori infections. We have developed a specific and sensitive enzyme-linked immunosorbent assay (ELISA) that detects serum immunoglobulin G antibodies directed against high molecular weight cell-associated proteins (HM-CAP) of C. pylori. In a blinded fashion we tested sera from 300 individuals and found that all of 147 HM-CAP ELISA-negative individuals were also negative for C. pylori, as documented by a negative urea breath test; also, 151 of 153 C. pylori-positive (by urea breath test) individuals were HM-CAP ELISA-positive. Campylobacter pylori was cultured from the two ELISA-negative but infected patients and these isolates did possess HM-CAP antigens, showing that these two individuals had failed to seroconvert. Thus, the specificity and positive predictive value of the HM-CAP ELISA were each 100%; the sensitivity of the assay was 98.7%, and the negative predictive value was 98.6%. The HM-CAP ELISA and the urea breath test both proved valuable for detecting C. pylori infection, the urea breath test being a more direct method whereas the ELISA is less expensive and easier to perform. Furthermore, the results of a serologic test such as the HM-CAP ELISA would not be influenced by recent ingestion of bismuth compounds or antimicrobial therapy, which might suppress C. pylori and cause a transient false-negative result in the urea breath test.

A strong positive correlation has been demonstrated between the (antral mucosal) presence of Campylobacter pylori and active duodenal and gastric ulceration. Moreover, both duodenal and gastric ulcers heal, and remain in remission, as a consequence of therapeutic measures which eradicate C. pylori. However, the Henle-Koch postulates have not been fulfilled, because C. pylori has not been shown to produce ulcers. As for the claim that ulcer disease represents an infection with C. pylori because therapeutic eradication heals ulcers, it has been shown that antibiotics and metronidazole, as well as bismuth subcitrate, exert antiulcer actions by mechanisms which do not involve their antibacterial effects. The association between C. pylori and ulcer disease, which was noted half a century ago, remains unexplained now as it did then.

Worldwide Campylobacter pylori is a major cause of active chronic gastritis in man. This curved spiraled microorganism can readily be detected within the mucusgel especially in the antrum, in particular in patients suffering from peptic ulcer disease or non-ulcer dyspepsia, rarely in individuals with normal gastroduodenal mucosa. Increasingly arguments are being presented in support of a pathogenetic role of C. pylori in non-ulcer dyspepsia and in peptic ulcer disease. There is a striking discordance between in vitro antibiotic sensitivity, and in vivo efficacy with respect to suppression or eradication of the organism. At present the combination of colloidal bismuth subcitrate and amoxicilline or tinidazole appears to be encouraging with respect to longterm eradication of this peculiar microorganism. Eradication by antibacterial treatment ultimately may result in histologic normalization of the gastric mucosa. To what extent peptic ulcer disease. There is a striking discordance between in vitro antibiotic sensitivity, and in.