Copyright ©The Author(s) 2000. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 15, 2000; 6(1): 20-31
Published online Feb 15, 2000. doi: 10.3748/wjg.v6.i1.20
Helicobacter pylori infection
Yvan Vandenplas
Yvan Vandenplas, Academisch Ziekenhuis Kinderen, Free University of Brussels, Brussels, Belgium
Yvan Vandenplas, male born on 1956-02-21 in Brussels, Belgium, graduated from the Free University of Brussels in 1981, and is now Head of the Department of Pediatrics, having more than 100 papers published.
Author contributions: Vandenplas Y solely contributed to this work.
Correspondence to: Yvan Vandenplas, Academic Children’s Hospit al, Free University of Brussels Laarbeeklaan 101, 1090 Brussels, Belgium.
Telephone: +32-2-4775780/81 Fax: +32-2-4775783
Received: May 19, 1999
Revised: August 2, 1999
Accepted: August 15, 1999
Published online: February 15, 2000

Key Words: Helicobacter pylori, gastritis, Helicobacter infection


Helicobacter pylori has been for many years a forgotten bacterium, since the first report on this spiral organism dated from the 19th century[1]. As early as in 1906, an association between a spiral organism and gastric carcinom a was suggested[2]. Doenges reported in 1938 that on autopsy not less than 40% of human stomachs were found to be invaded by spiral organisms[3]. In 1940, the therapeutic effect of bismuth in patients with peptic ulcer in the presence of spiral bacteria in the stomach was reported[4]. Then, interest in this bacterium decreased. In 1982, two Australian researchers, Marshall and Warren, rediscovered the microbe[5], and called it at first Campylobacter pylori, later Helicobacter pylori. Today, the complete genome (1590 genes) of H. pylori has been unmasked[6] and published on the internet (, probably paving the way for sequencing the genome of other organisms, including that of humans within a few years[7].

WHY IS Helicobacter pylori SO IMPORTANT?

There is unequivocal evidence that H. pylori can be considered as a healthcare issue because of the mortality associated with the infection, due to the risk of ulcer bleeding and gastric cancer. Infection with H. pylori results in the development of gastritis in all infected humans, including children and adolescents[8]. Peptic ulcer disease is a major cause of morbidity and distal gastric adenocarcinoma, which is the second biggest cancer killer worldwide[9]. However, the majority of infected individuals remain free of symptoms throughout their lifetime; only a small number present with peptic ulcer disease (lifetime risk 15%), and an even smaller proportion will develop gastric neoplasms including ( mucosa-associated lymphoid tissue) lymphoma and adenocarcinoma (lifetime risk 0.1%)[10]. Overall, H. pylori can be discovered in 92% of children with duodenal ulcers and in 25% of children with gastric ulcers[11]. H. pylori infection is contracted primarily in childhood, and infection from childhood appears to enhance the risk for carcinogenesis[12].


The microaerophilic, gram-negative, urease-producing H. pylori fulfills each of Koch’s postulates[8]. In the normal living form, it is a spiral-s haped bacterium, but the coccoid form can also cause lesions. The bacterium colonizes the stomach of man and induces severe mucosal inflammation and a local and systemic immune response. It is capable of changing its membrane potential at external pH from 3.0 to 7.0 in order to maintain a neutral internal pH[13]. Not all H. pylori strains are created equally[14]; and not all are associated with clinical symptoms.

Some virulence factors such as urease and flagella are present in all strains and are necessary for pathogenesis and colonization. Flagella, and thus motility, are needed for persistent gastric colonization[15]. The gene FlbA is needed for flagellar expression[16]. Enzymes produced by H. pylori have mostly metabolic, antioxidant and toxic properties[17]; most of these are produced by all isolates tested. Urease is required to establish infection, and is located intra and extra-cellularly[15]. It is a nickel-containing metallo-enzyme, consisting of two structural subunits, UreA and UreB[18]. Urease is primarily a cytoplasmic enzyme[19], and hydrolyzes urea to bicarbonate and ammonia, resulting in a net increase in the ambient pH. Ammonia is a nutrient for the bacteria, and causes lesions to the gastric epithelium by many different mechanisms[20]. Surface urease helps protect against acid exposure, but it is as yet unclear why it is found on bacteria deep underneath gastric mucus where the pH is thought to be neutral. Because there is no obvious urease export machinery, it has been suggested that some bacteria undergo autolysis, which released proteins, including active urease are absorbed onto the surface of remaining intact bacteria[19,21]. Urease might function as an adhesin, although this suggestion has also been contradicted[22]. Ureasest imulates the release of a variety inflammatory cytokines including interleukin-beta, interleukin-6, tumor necrosis factor-alfa, and chemokines such as interleukin-8[23]. Although the exact mechanism by which urease functions in the pathogenesis of gastric disease remains unclear, it is likely that urease is an important virulence factor.

H. pylori can produce different kinds of phospholipases weakening the hydrop hobicity of the gastric mucous and mucosa. Phospholipase can also generate ulcer ogenic substances[24]. Many other enzymes, such as mucinase, neuraminidase, fucosidase, alcohol dehydrogenase, etc. have been reported[20].

The vacuolating cytotoxin A (VacA) gene is present in all strains, but is only expressed in 50% of H. pylori isolates[25]. The vacuolating activity of VacA is increased by exposure to acidic pH values[26]. The vacuoles a re formed by merging of late endosomes and the mechanism causing this has been determined[27]. The VacA gene exhibits different allelic combinations. Strains with the gene s1/m1 have the highest levels of cytotoxic activity; colonize the stomach more densely and are correlated with peptic ulcer, atrophic gastritis and gastric cancer; s2/m2 strains have no toxic activity[20,28].

Other virulence factors, such as “cytotoxic-associated gene A” (cagA)encoded proteins are only found in a proportion of the strains. This might explain why not all strains are associated with clinical symptoms, although both cagA and the s1 vacA allele are unreliable as single markers in determining the risk of deve loping peptic ulcer disease[29]. The cagA protein is a cryptic 128 kDa immunodominant antigen produced by H. pylori. CagA is a marker for a larger cluster of genes (40 different genes[20]carried on a pathogenicity island that exhibits variability between strains[30].CagA+ strains produce increased amounts of interleukin 8[30]. Gastric atrophy, duodenal ulceration and gastric carcinoma are more common in patients infected with CagA+ than with Cag A-strains[31]. CagA negative strains are very rare in some Far East countries such as China and Korea but frequent in some other areas such as Hong Kong, and are reported to be not a marker of specific disease in these regions[32]. However, allelic variations in the cagA protein are found in different parts of the world. In Western countries, cagA positive strains are associated with gastric atrophy and peptic ulcer disease[33]. But, there appears also to be no association between cagA and clinical symptoms or ulcers in children[32,34]. Other putative virulence determinants are being discovered, such as the neutrophil-activating protein (napA) gene, a gene “induced by contact with epithelium” ( iceA1 ), etc[20]. However, according to the recent data, it is suggested that there is no correlation between the degree of inflammation and the presence of the cag-pathogenicity island, cytotoxin production, vacA alleles associated with cytotoxin expression in children[35].

Auto-immunity and host mimicry by expression of blood group antigens may be a relevant phenomenon. Adhesion of H. pylori is nonspecific although preferential to epithelial cells and is enhanced at low pH, inducing epithelial cell reorganization and causing deep invagination of the apical membrane, explaining resistance to topical antibiotic treatment[36]. One host receptor for adhesion appears to be a blood group O antigen, possibly explaining why ulcers are more common in people with this blood group[37]. The H. pylori lipopolysac charide (LPS) or endotoxin is unusually biologically inert compared with that from other bacteria. However, the mechanisms by which H. pylori LPS stimulates cells appears similar to that of other types of bacterial LPS[38].H. pylori LPS often contains Lewis x and Lewis y blood group antigens that are identical to those occurring in the gastric mucosa[39]. H. pylori presents bacterial epitopes to the host which are similar to the structure on host gastric epithelium; therefore, the host reacts with an auto-antibody response recognizing gastric mucosa inducing atrophic gastritis[40]. Patients with a large parietal cell mass and high acid secretion will have a predominantly antral gastritis, predisposing to duodenal ulcer[41]. People with a small parietal mass and low acid output (or people on proton pomp inhibitors) will be more prone to develop atrophic gastritis and gastric malignancy[41]. The variability in occurrence of gastric cancer in different parts of the world may only be partly explained by the prevalence of H. pylori. Apoptosis of gastric epithelial cells is increased in H. pylori infection, stimulating crypt cell proliferation, increasing the risk for mutagenesis[42]. Atrophic gastritis enhances the development of intestinal metaplasia, and is related to the intestinal type of gastric carcinoma but not to diffuse gastric carcinoma[43]. Intestinal metaplasia is related to atrophic gastritis, which is on its turn related to H. pylori infection.


H. pylori infection in children is mostly asymptomatic and not associated with specific gastrointestinal symptoms[44]. H. pylori gastritis, in the absence of duodenal ulcer, does not appear to be associated with specific symptoms[11,45-49]. After eradication of H. pylori infection, symptoms are improved only in those children with duodenal disease[46]. Children with H. pylori gastritis cannot be distinguished from noninfected children on the basis of initial symptoms[45,49]. Many studies failed to demonstrate a difference in H. pylori infection rate in children with or without recurrent abdominal pain[11,49-51], although others did find this association[52]. Recurrent abdominal pain would occur during the acute phase of H. pylori infection[52]. It is unclear whether children with recurrent abdominal pain with H. pylori represent a different entity to those without H. pylori. H. pylori positive children might more often have pain related to meals than H. pylori negative children. Ulcer-like symptoms may be more closely associated with the infection than other symptom complexes[53].

In adults, a significantly lower H. pylori prevalence was reported in patients with gastro-esophageal reflux disease[54]. The role of H. pylori in duodenogastric reflux is unclear. A decreased mean acid output in subjects with H. pylori gastritis might explain the inverse relation between reflux and H. pylori. Heartburn and epigastric pain might be more frequent in H. pylori infected patients. Pooled data from 18 studies suggest that the prevalence of H. pylori was greater in patients with dyspepsia than in controls[53]. It is unclear whether H. pylori changes gastric emptying rate or not, although most data have suggested that gastric emptying is normal[55-57]. In adults, H. pylori is also beyond any doubt associated with an incre ased incidence of gastrointestinal cancer. However, the high prevalence of early H. pylori infection and chronic gastritis in children contrasts with the rarity of gastric cancer in black African[58]. Nevertheless, acquisition in infancy is in general considered to be a significant risk factor to develop gastric carcinoma[48].

Similar to other chronic inflammatory conditions, infection with H. pylori has been linked to reduced growth[59-65], although socioeconomic factors confuse the issue. Tumor necrosis factor-alpha is inversely correlated with growth, and is increased in H. pylori[66]. However, studies have also failed to find differences in hemoglobin, leukocytes, thrombocytes, weight and height[50,67]. Differences in growth seem to be limited to the developing countries[62,63]. It has been speculated that H. pylori acquired in infancy could be “the key that opens the door” to enteric infection leading to recurrent diarrhea, malnutrition and growth failure[62]. There is, however, no difference in diarrhea prevalence in relation to H. pylori status[68]. After control for socioeconomic status, there is no difference in the height of adults with and without H. pylori. H. pylori seropositivity is related to a late menarche[69,70]. Socioeconomic status and malnutrition does not explain late menarche, since elevated body mass index is also independently associated with H. pylori in the same population[70]. Incidentally, anemia, hemoptysis and vertigo have been reported[71,72].

The association of H. pylori with extra-digestive diseases, such as functional vascular diseases and skin and endocrine autoimmune diseases, has been described[73-76]. An interesting relationship between seropositivity to H. pylori, serum glucose and non-insulin dependent diabetes mellitus is worthy of further attention. Recent studies suggest that the association between H. pylori and coronary heart disease is rather weak[65,73]. Primary Raynaud ‘s phenomenon, observed in young women, which is defined by an intermittent vas ospasm of the arterioles of the distal limbs that occurs mostly following exposure to cold or emotional stimuli, may be related to H. pylori in some cases[74]. H. pylori may in addition cause headache[74]. Vasoactive substances, such as cytokines (interleukins, interferon, gamma, TNF-alpha), prostaglandins, leukotrienes, oxyradicals, C-reactive protein and fibrinogen are released in chronic infection[74]. Henoch-Sch-nlein purpura and Sj-gren’s syndrome have been correlated with the bacterium. Many patients with autoimmune thyroid diseases a re infected with type I cytotoxic cagA-positive strains[75]. Rosacea and recurrent urticaria may also be associated with H. pylori infection[76]. Alopecia areata is related to atrophic gastritis and pernicious anemia, and thus with H. pylori[74]. Until now, H. pylori has not yet been reported to cause hepatitis in human. Although a mice Helicobacter species has been reported to cause hepatitis in germfree mice, and H. pylori has been identified in the gallbladders of human[77,78]. An Italian group showed a positive correlation between food allergy and H. pylori[79].

H. pylori in infants and children

Independent risk factors for H. pylori infection in infants and children include living in lower socioeconomic and overcrowded circumstances and sharing a bed with a parent. Human lactoferrin can support H. pylori growth in vitro and H. pylori binding lactoferrin has now been identified. Infants born to seropositive mothers passively acquire maternal H. pylori IgG[80,81]. Transplacentally transferred maternal anti-H. pylori IgG lasts until about the third month of life in most infants and disappears from nearly all by 6 months[80]. IgA in mother’s milk can protect the infant from H. pylori infection[82]. However, whether breast feeding is related to a low or high prevalence of H. pylori infection in infants remains unclear[80,83,84] (protective effect of mother’s milk versus intimate contact between infant and H. pylori positive mother). At the age of 14 months, 7.5% of infants in a p opulation with a seroprevalence in 62% of young adults, had acquired H. pylori , an event demonstrated by a rise in IgM, quickly disappearing and preceding IgG[80,85,86]. In Belgium, less than 1% of infants are seropositive at the age of 1 year[87] (seropositivity in young adults is about 30%)[87,88]. In Finland, 4% of children under the age of 7 years have a positive serology[89].

Approximately 30% of 53 children ( 16/53 ) with dyspepsia were infected with H. pylori in the antrum, and about half of them a cytotoxic train was present (anti-Cag A antibodies in 64% and anti-vacA antibodies in 43%)[90]. In only 6/53 children, the H. pylori was also detected in the gastric body[90]. Clinical evaluation showed a significant difference in favor of subjects positive for H. pylori only for epigastric burning and/or pain[90].

Clinical symptoms associated with H. pylori infection have been reported in patients with human immunodeficiency virus ( HIV )-1[91,92]. Although H. pylori has been said to be rare in HIV-1 infected individuals (e.g., be cause of the repetitive and multiple administrations of antibiotics and immunoglobulins)[92], recent data suggest that the prevalence of H. pylori infection in HIV-1 infected children is comparable to the prevalence in the non-infected control population[91].

Diagnostic and screening tools

A large number of invasive and non-invasive methods have been used to diagnose H. pylori infection in humans[93]. Culture of the organism is a standard method for the diagnosis of bacterial infection. H. pylori can be cultured from gastric biopsies. Culture of H. pylori requires a microaerobic atmosphere of 5% oxygen with 5%-10% CO2. When H. pylori is cultivated on biopsy, sensitivity to antibiotics should be tested[94]. Whether coccoidal forms also grow in blood agar or not is controversial[95,96].

Histologic examination of Giemsa or Warthin-Starry stained gastric biopsy specimens is widely used for the diagnosis. The Sydney criteria for the classification of gastritis have been revised[97]. Gastric biopsy urease tests make use of a change in color of phenol red which is present in the medium because of a pH increase related to the digestion of urea by the urease. Four rapid urease tests are available commercially: CLO-test (Delta West Ltd, Bentley, Australia ), Hpfast ( GI Supply, Philadelphia, USA) and PyloriTek (Serin Research Corporation, Elkhart, USA ), Jatrox ( Röhm Pharma GMBH, Weiterstadt, Germany), although many hospitals prepare their own urease tests. These commercial tests have a high specificity and sensitivity and provide comparable results[98]. PyloriTek has a shorter reading time than CLO-test[99]. Antral and corpus biopsies provide comparable results, and in combination they increase the sensitivity by 4.3%[100]. Although these biopsy urease tests have a high degree of sensitivity in adults, false negative results are common in children, possibly because of a smaller bacterial load[101].

Molecular methods for biopsy material or other biological samples and current PCR methods for molecular fingerprinting of H. pylori have been developed[102,103]. PCR techniques can quantitate the bacterial load in gastric samples[103,104]. Several molecular methods have been applied to typing H. pylori isolates and demonstrating their genomic diversity. Unfortunately, all these tests necessitate endoscopy[103].

Magnetic beads coated with anti-H. pylori rabbit antibodies permit detection of less than 10-million organisms per gram of feces[105]. PCR-detect ion of H. pylori in feces is hindered by the presence of inhibitors of Taq polymerase, complex polysaccharides which can be eliminated by filtration on Qiagen and dilution. But, immunomagnetic separation-PCR is recently reported to be simple, rapid and reliable[106]. Nevertheless, the technique is not available as routine.

The ability to detect antibodies in saliva rather than in serum would improve antibody tests by avoiding the need for blood collection[107]. Sensitivity ( 84%-93% ) and specificity ( 70%-82%) are too low, but comparable to rapid whole blood diagnostic tests[107-109]. The discovery of the potential importance of the cagA-pathogenicity island has stimulated interest in the specific detection of the CagA protein.

Serologic testing for IgG antibodies against H. pylori requires validation of the assay in children, since antibody levels differ in children and adults, probably because of the duration of infection and the differences in bacterial load[85,106,110,111]. In addition, commercially available serologic tests demonstrate lower accuracy compared with testing in a research setting[112], with sometimes up 33% false positive and 25% false negative results[111,113,114]. Serology is more and more frequently reported to be unsatisfactory for screening for H. pylori infection in children[106,111]. Testing should not rely on office tests[94]. After eradication, there is a slow decline in antibody titer. Many patients remain seropositive 1 year after eradication[115]. At acquisition of the infection, there is a temporary rise in IgM[80,85,86,111,116]. IgA is also reported to be a useful serologic screening tool[117]. Immunoblot has become the reference method used to confirm doubtful results[118]. Specific serologies for cytoxic strains may be helpful in selecting patients for treatment[90].

Carbon-13 and C-14 breath tests are based on the fact that urease from H. pylori will hydrolyze the ingested labeled urea into ammonia and labeled bicarbonate, which is exhaled as labeled carbon dioxide[18]. Whether a test meal should be given, or whether the labeled urea should simply be given after a period of fasting, or whether addition of citric acid would be beneficial is not clear[119-121]. A standardized and simplified C-13 breath test was recently described in children[122]. The high sensitivity and specificity of the 13 C-breath test in the detection of H. pylori infection in children has been unequivocally demonstrated[90,123,124]. The best cut off value is obtained after 30 minutes[120]. False positive results can occur because of the presence of other urease containing gastric bacteria or because of extra- gastric bacterial urea metabolism (seldom). False negative results are mainly due to fast gastric emptying or previously administered urease-inhibiting drugs, such as antibiotics or bismuth-containing salts. There is a close correlation between the urea breath test and the intragastric bacterial load[100,125], which is on its turn related to the severity of the gastritis. Unfortunately, carbon-13 breath tests are still expensive in many parts of the world. A less expensive method for the analysis of 13C-labeled carbon dioxide is nondispersive infrared spectrometry, with a comparable sensitivity and specificity[126]. But, infrared spectrometry necessitates larger volumes of expired air, making the technique less suitable for (small) children. Alternatively, measurement of 14C-labeled carbon dioxide with a scintillation counter is relatively inexpensive[127]. Although the dose required for one test is not greater than the natural background radiation, the use of 14C is considered unethical in pregnant women, adolescents and children because of its extremely long half-life, since 14C may be incorporated into the bicarbonate pool[128]. The urea breath test is in general accepted to be the most reliable noninvasive diagnostic method[90,129]. The urea breath test detects only current infection and can be used to screen for H. pylori infection and as the sole method for assessing eradication, and to evaluate treatment efficacy[129].


The prevalence of H. pylori infection in many populations and/or subgroups is currently well documented. The overall prevalence of H. pylori in children is 10% in developed countries but can be as high as 30%-40% in children from lower socioeconomic classes[48]. In developing countries, the prevalence of H. pylori in children ranges from 80% to 100%[48]. Like many other childhood bacterial infections, H. pylori is most frequently acquired in the preschool age group, with the associated effects of family size, clustering in families, low socioeconomic status and education and variable risks associated with gender[89,130,131]. Recent sociocultural changes may result in changes in infection rates in children[132], which is an important argument for the cohort effect. In general, it is thought that spontaneous eradication of H. pylori infection is extremely rare[133,134]. However, recently some authors have suggested that from 1.5% up to 10% or even 20% of spontaneous eradication occurs in a period of 6 months during childhood[111,135,136]. Although, others still report a zero incidence of seroreversion[89]. These discrepancies may, however, be related to the methodology (serology versus urea breath test). Recent epidemiologic data suggest that serology underestimates H. pylori infection in children[106,111], and antibodies may persist a lthough H. pylori disappeared.

In the developed world, acquisition by adults and children is approximately 1% to 3% per decade[131,136,137], which will result in a dramatic decrease in H. pylori infection in that part of the world in the coming decades. In The Netherlands, about 40% of the 60-69-year-old population is seropositive[137]; since the prevalence in adolescents is below 10%[138], it can be speculated that the seropositivity of this cohort will probably not be higher than 25% when reaching the age of 70 years. In Gambia, the prevalence of a positive breath test at the age of 3 months is about 19%, increasing to 84% at 30 months[111].

Re-infection probably does not occur frequently and is, in many cases, consider ed recrudescence after treatment failure[139]. Re-infection rates vary strongly with the effectiveness of the treatment protocol[139,140]. In Chile, re-infection occurred in 4.2% after 1 year, with a treatment protocol that was 82% effective[141,142]. Annual user-relapse rate in children wit h duodenal ulcer in whom H. pylori was eradicated was reported to be 9%[143]. The percentage of re-infection does not appear to be much higher in developing countries than in developed regions. As a consequence, there is little reason for treating an entire family to prevent re- infection, although spread from one adult to another has been suggested[144]. Others do suggest family treatment[183]. It seems more likely that re-infection comes from an external source. Of course, a more detailed specification of the H. pylori strain will contribute to the answer whether re-infection rather than relapse occurs. Repetitive extragenetic palindromic-PCR can group isolates into clusters that appear to have a different clinical expression[102]. Oligonucleotide probes containing short repetitive sequence motifs can differentiate between different isolates of H. pylori[146].

The major mode(s) of transmission of H. pylori are still unknown, oral-oral, gastro-oral and fecal-oral have been proposed[147,148]. Infected parents, especially mothers, may play a key role in transmission of H. pylori within families[81,149]. Houseflies could serve as vectors for H. pylori[150]. Pets have been suggested as well as contradicted to be vectors[151]. There is considerable evidence of transmission of oral bacteria between spouses and between family members[144]. Vomiting and gastroesophageal reflux might also be a mode of oral-oral contamination[152]. Mode of spread remains an active area of study, with water as a source of contamination still of potential interest. The coccoid form can cause cellular changes similar to the spiral form[153], and may serve as the infectious form in environmental sources such as water[154]. Studies on external water sources in Peru revealed PCR products of H. pylori in the municipal water, increasing 12 -times the risk for infection[155]. The examples of studies in Peru and Chile suggest a role for water as a vehicle, but it does not seem to be the main route of acquisition since many studies in Korea[132], Taiwan, or Turkey do not support this hypothesis.

Host response to H. pylori

Another factor contributing to the heterogenecity of H. pylori associated symptoms is the variability in host response to the infection. Duodenal bicarbonate secretion is decreased in ulcer patients, and returns to normal after eradication of H. pylori[156,157]. Acute H. pylori infection has been as so ciated with hypochlorhydria, possibly by stimulating the production of a histamine-3 receptor agonist, which inhibits gastric acid output. In contradiction to this finding is the observation that the same histamine-3 receptor agonist can stimulate parietal cells to produce acid via the histamine-2 receptor[158]. Identification of Lewis carbohydrate structures on H. pylori lipopolys accharide may provide an explanation for the development of autoantibodies, reacting with gastric mucosa (“molecular mimicry”)[159].


Currently, there are no guidelines on the need to treat children[48]. The regimens that have been studied to date have used bismuth preparations, H2-receptor antagonists, ranitidine bismuth citrate, proton pump inhibitors and various antibiotics. The goal of any treatment should achieve an eradication rate of over 80% on a rigorous intention-to-treat basis[94]. Most European H. pylori study groups now recommend (in adults) a triple regimen: a twice daily dose of proton pump inhibitor (PPI) in combination with two antibiotics [from the following 3 groups: clarithromycin; amoxicillin; nitroimidazoles (metron idazole or tinidazole)] for 1 week[94,160,161]. There are no specificr ecommendations for children yet[162]. It has been hypothesized that combination therapy is more effective because of the synergistic mechanisms between different drugs. The requirement is for a simple, well-tolerated regimen, with which it is easy to comply with, and is cost-effective. In a recent Irish study in children, the therapeutic approach consisted of colloidal bismuth subcitrate (480 mg/1.73 m2 body surface for 4 weeks) in combination with amoxicillin (750 mg/ day for 2 weeks) or metronidazole ( 20 mg/kg / day for 2 weeks)[120]. In most European countries, eradication treatment in children consists usually of a PPI in combination with amoxicillin and either clarithromycin or nitroimidazole, based on the sensitivity of the prevailing strains. Although antibiograms are needed, there seems to be major discrepancy between in vitro testing and in vivo efficacy. Resistance to amoxicillin has recently been reported, but seems rare[163]. Resistance to macrolides is rising with increasing use of the drugs, and for both macrolides and nitroimidazoles there is a huge regional variation in resistance patterns. Especially the determination of resistance to metronidazole may be relevant in regions with a high percentage of resistance[164].

Bismuth triple therapy continues to achieve high eradication rates worldwide (78%-89%). Side effects leading to diminished patient compliance and the marked decline of eradication efficacy in cases of metronidazole resistance are considered to be the major drawbacks of this therapy. PPI dual therapy is better tolerate d with fewer side effects than is bismuth triple therapy. The mean eradication rates vary from 55% to 75%, and the extremes lie between 24% and 93%. PPI triple therapies have been shown to be very effective against H. pylori with an eradication rate 80%-90%. Eradication rate in children with 2 weeks of treatment with clarithromycin, amoxicillin and proton pump inhibitors (omeprazole or lansopr azole) is reported to be 75% and 92%, respectively[165,166]. Omeprazole, clarithromycin and metronidazole or tinidazole for 7 days are reported to cause eradication in 87% and 89%[167,168]. Dual therapy for 2 weeks with omeprazole and amoxicillin causes eradication in 70% of infected children, whereas a ddition of clarithromycin for 2 weeks increases the eradication rate up to 92%[169]. Amoxicillin, bismuth and metronidazole were reported to eradicate H. pylori in 96% of infected children[143]. Quadruple therapy leads to a mean eradication rate of 96%. Thus, based on efficacy PPI triple or bismuth triple therapy are recommended as first-line treatment[170]. The cost of PPI versus bismuth should be considered. However, compliance strongly influence the eradication rate, and may explain why, in contradiction to experience in adults, in children two drugs for 2 weeks are sometimes found to be equally effective than triple therapy for 1 week[171].

Eradication therapy is not recommended for all H. pylori infected adults and children[162]. However, the complex relationship between H. pylori and gastrointestinal cancer might stimulate physicians to prescribe eradication treatment, even in the absence of scientific evidence, especially in countries with a strong impact of legislation on health care, as in the case in the US in children, not one randomized prospective placebo-controlled study had been conduct ed. Whether children with symptomatic H. pylori gastritis alone will benefit from treatment is debated[90,121]. Well-designed clinical trials showing a therapeutic gain of H. pylori treatment over placebo are still missing, with the exception in duodenal ulcer patients. The cost-benefit ratio of avoiding endoscopy in dyspeptic patients is only worthwhile considering if the cost of end oscopy is greater than $500 USD[172], as is the case in the USA; while the cost of upper gastrointestinal tract endoscopy in Belgium and Finland is only about $100 and $170 USD, respectively[173].

Nevertheless, recommendations differ in Europe and the USA. The European consensus states that scientific evidence for the improvement of functional dyspepsia is equivocal, but the overall evaluation taking into account the expected benefit on the gastritis status makes it worthwhile to consider eradication therapy in such patients. In Europe, it is accepted, although not unanimously, that young patients, aged below 45 years, without alarm symptoms (anemia, weight loss, dysphagia, palpable mass, malabsorption, etc.) and who test positive for H. pylori for the first time with validated serology or breath test, can be treated with eradication therapy without further investigations (thus without endoscopy)[94,160]. However, in the USA, the present consensus states that there is no scientific evidence to recommend treatment for H. pylori in the absence of an established peptic ulcer disease[156]. As a consequence, according to the North American consensus, non-invasive testing cannot replace endoscopy in t he initial diagnosis of H. pylori related gastrointestinal diseases ( not in children either)[174]. Eradication of H. pylori in patients who do not benefit from it may unnecessarily increase the risk of resistance of H. pylori to antibiotics.

H. pylori and non-steroid anti-inflammatory drugs (NSAIDs) are both ulcerogens; however, NSAIDs are not frequently prescribed in children, and moreover, there seems to be no cooperative effect between them. Consequently, eradication of H. pylori prior to NSAID administration is not recommended in the USA. In Europe, eradication of H. pylori before NSAIDs is considered “advisable”.

Elimination of H. pylori increases the risk of developing gastroesophageal reflux and reflux esophagitis[157,175]. H. pylori eradication results in a marked decrease in the pH-increasing effect of omeprazole and ranitidine[176]. Nevertheless, long-term acid suppressive therapy with proton pump in hibitors ( and to a lesser extent with H2-antagonists) for reflux disease in H. pylori positive patients enhances the development of atrophic gastritis if H. pylori has not been eradicated beforehand[177,178].

Eradication of H. pylori can be demonstrated by normalization of histology and negative culture of gastric biopsies, or with the use of urea breath tests[94]. With respect to serology, a 50% fall in antibody titers is indicative of successful elimination. However, this usually requires up to 6 months to occur[179]. When follow-up tests for eradication of H. pylori are necessary, they should not be made earlier than 4 weeks after cessation of treatment[94]. The bacterial load could influence the success rate of eradicating treatment[180].

Knowledge of the H. pylori genome provides major new insights into many aspects. Conversion of pyruvate to acetyl-CoA uses an unusual enzyme, only previously found in free-living bacteria from extreme environments[181]and the genome sequence shows that acetyl-CoA is likely to be a crucial intermediary in several biosynthetic pathways. Therefore, blocking the enzyme should allow effective and selective drug activity against H. pylori. The same is true for many other enzymes.


Study of the H. pylori outer membrane is important for both understanding the pathogenicity but also for development of vaccines since the outer membrane is involved in adherence to the host epithelium and stimulation of the host immune response. Vaccines should be able to confer preventive and curative immunity on humans. Oral immunization with a recombinant urease given in the absence of a mucosal adjuvant has been assessed unsuccessfully in H. pylori infected volunteers[182]. However, recently, the recombinant H. pylori urease was given with an E. coli heat-lable toxin, provoking diarrhea in the majority of the volunteers, a side-effect which disappeared when the dose was reduced, but also showing an increase in urease specific IgA producing cells and a decrease in the density of gastric colonization by H. pylori[183].

IgA antibodies are expected to play a prominent role in protection, since H. pylori is a non-invasive pathogen at the luminal surface of the gastric mucosa. This hypothesis has been supported by the observation that milk IgA protects infants against H. pylori infection[82]. IgA and immunoglobulin G1 (I gG1) depend on T-helper type 2 (Th2) cells. According to different recent experiments, immunization is associated with an elevation of IgG1 levels, indicative of a Th2 cellular immune response, which might be a significant mechanism[184-186]. The field of vaccination is still very controversial, and is being extensively studied.


Helicobacter pylori infection is worldwide one of the most frequent infectious diseases. There is a huge discrepancy in prevalence and incidence between the industrialized countries and the rest of the world (Africa, Asia, South-America). Infection occurs mainly in children. Well-designed studies to identify thos e infected children who are at risk of developing complications or have symptoms due to the infection are still lacking[171]. Because of the cohort-effect which is related to the socio-economic status and/or hygienic circumstances, the annual infection rate in the Western world is dramatically decreasing. If this observation is confirmed, it can be speculated that a decrease in incidence of peptic ulcer disease and gastric cancer may occur in the more industrialized countries during the next decades. However, duodenal ulcer and gastric cancer are only related to some more virulent strains. Many children remain asymptomatic, and a clear relation between H. pylori and symptoms has only been demonstrated for ulcer-related symptoms. In addition, peptic ulcers are rare in childhood. Treatment of H. pylori is indicated in duodenal ulcer diseases. The relation between chronic abdominal pain, functional dyspepsia, and H. pylori is unclear.

Screening tests, including serology or the urea breath test, are of interest for epidemiological studies. The urea breath test evaluates the actual colonization; serum antibodies might persist after eradication, which is only rarely spontaneous. According to the European consensus, eradication therapy can be considered in a child with functional dyspepsia and positive screening test. According to the North American consensus, treatment is only recommended in the presence of ulcer, necessitating endoscopy.

H. pylori strains are not created equal since important virulence factors are not detectable in all strains. The continuous decline of H. pylori prevalence as a result of changes in living conditions and active treatment is not unanimously considered to be beneficial[14]. Unfortunately, screening tests rely on virulence factors which are detectable in all strains. Vaccines are not expected to be available in the near future.

Nevertheless, improvement of the socio-economic status and hygienic circumstances in all countries will result in a dramatic decrease of H. pylori.


Edited by Ma JY

1.  Bizzozzero B. Uber die sclauf rmigen Drüsen des Magendarmkanals und die Beziehungen ihres Epithels zu dem Oberfl chenepithel der Schlerimhaut. Arch Mikr Anat. 1893;23:82-152.  [PubMed]  [DOI]
2.  Krienitz W. Uber das Auftreten von Spirochaeten verschiedener Form im Mageninhalt bei Carcinoma ventriculi. Dtsch Med Wschr. 1906;22:872.  [PubMed]  [DOI]
3.  Doenges JL. Spirochetes in the gastric glands of macacus rhesus and humans without definite history of related disease. Proc SocExp Med Biol. 1938;38:536-538.  [PubMed]  [DOI]
4.  Gorham F. Editorial. Am J Dig Dis. 1940;7:445.  [PubMed]  [DOI]
5.  Marshall BJ, Warren JR. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983;1:1273-1275.  [PubMed]  [DOI]
6.  Tomb JF, White O, Kerlavage AR, Clayton RA, Sutton GG, Fleischmann RD, Ketchum KA, Klenk HP, Gill S, Dougherty BA. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature. 1997;388:539-547.  [PubMed]  [DOI]
7.  Schlessinger D. Genome sequencing projects. Nat Med. 1995;1:866-868.  [PubMed]  [DOI]
8.  Bourke B, Jones N, Sherman P. Helicobacter pylori infection and peptic ulcer disease in children. Pediatr Infect Dis J. 1996;15:1-13.  [PubMed]  [DOI]
9.  Atherton JC. Helicobacter pylori unmasked--the complete genome sequence. Eur J Gastroenterol Hepatol. 1997;9:1137-1140.  [PubMed]  [DOI]
10.  Fennerty MB. Is the only good H. pylori a dead H. pylori. Gastroenterology. 1996;111:1773-1774.  [PubMed]  [DOI]
11.  Macarthur C, Saunders N, Feldman W. Helicobacter pylori, gastroduodenal disease, and recurrent abdominal pain in children. JAMA. 1995;273:729-734.  [PubMed]  [DOI]
12.  Blaser MJ, Chyou PH, Nomura A. Age at establishment of Helicobacter pylori infection and gastric carcinoma, gastric ulcer, and duodenal ulcer risk. Cancer Res. 1995;55:562-565.  [PubMed]  [DOI]
13.  Scott DR, Weeks D, Hong C, Postius S, Melchers K, Sachs G. The role of internal urease in acid resistance of Helicobacter pylori. Gastroenterology. 1998;114:58-70.  [PubMed]  [DOI]
14.  Blaser MJ. Not all Helicobacter pylori strains are created equal: should all be eliminated. Lancet. 1997;349:1020-1022.  [PubMed]  [DOI]
15.  Eaton KA, Suerbaum S, Josenhans C, Krakowka S. Colonization of gnotobiotic piglets by Helicobacter pylori deficient in two flagellin genes. Infect Immun. 1996;64:2445-2448.  [PubMed]  [DOI]
16.  Schmitz A, Josenhans C, Suerbaum S. Cloning and characterization of the Helicobacter pylori flbA gene, which codes for a membrane protein involved in coordinated expression of flagellar genes. J Bacteriol. 1997;179:987-997.  [PubMed]  [DOI]
17.  Nilius M, Malfertheiner P. Helicobacter pylori enzymes. Aliment Pharmacol Ther. 1996;10 Suppl 1:65-71.  [PubMed]  [DOI]
18.  Graham DY, Klein PD. What you should know about the methods, problems, interpretations, and uses of urea breath tests. Am J Gastroenterol. 1991;86:1118-1122.  [PubMed]  [DOI]
19.  Phadnis SH, Parlow MH, Levy M, Ilver D, Caulkins CM, Connors JB, Dunn BE. Surface localization of Helicobacter pylori urease and a heat shock protein homolog requires bacterial autolysis. Infect Immun. 1996;64:905-912.  [PubMed]  [DOI]
20.  Figura N. Are Helicobacter pylori differences important in the development of Helicobacter pylori-related diseases. Ital J Gastroenterol Hepatol. 1997;29:367-374.  [PubMed]  [DOI]
21.  Dunn BE, Vakil NB, Schneider BG, Miller MM, Zitzer JB, Peutz T, Phadnis SH. Localization of Helicobacter pylori urease and heat shock protein in human gastric biopsies. Infect Immun. 1997;65:1181-1188.  [PubMed]  [DOI]
22.  Clyne M, Drumm B. The urease enzyme of Helicobacter pylori does not function as an adhesin. Infect Immun. 1996;64:2817-2820.  [PubMed]  [DOI]
23.  Harris PR, Mobley HL, Perez-Perez GI, Blaser MJ, Smith PD. Helicobacter pylori urease is a potent stimulus of mononuclear phagocyte activation and inflammatory cytokine production. Gastroenterology. 1996;111:419-425.  [PubMed]  [DOI]
24.  Langton SR, Cesareo SD. Helicobacter pylori associated phospholipase A2 activity: a factor in peptic ulcer production. J Clin Pathol. 1992;45:221-224.  [PubMed]  [DOI]
25.  Atherton JC, Peek RM, Tham KT, Cover TL, Blaser MJ. Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology. 1997;112:92-99.  [PubMed]  [DOI]
26.  de Bernard M, Papini E, de Filippis V, Gottardi E, Telford J, Manetti R, Fontana A, Rappuoli R, Montecucco C. Low pH activates the vacuolating toxin of Helicobacter pylori, which becomes acid and pepsin resistant. J Biol Chem. 1995;270:23937-23940.  [PubMed]  [DOI]
27.  Papini E, Satin B, Bucci C, de Bernard M, Telford JL, Manetti R, Rappuoli R, Zerial M, Montecucco C. The small GTP binding protein rab7 is essential for cellular vacuolation induced by Helicobacter pylori cytotoxin. EMBO J. 1997;16:15-24.  [PubMed]  [DOI]
28.  Atherton JC, Tham KT, Peek RM, Cover TL, Blaser MJ. Density of Helicobacter pylori infection in vivo as assessed by quantitative culture and histology. J Infect Dis. 1996;174:552-556.  [PubMed]  [DOI]
29.  Gunn MC, Stephens JC, Stewart JD, Rathbone BJ. Detection and typing of the virulence determinants cagA and vacA of Helicobacter pylori directly from biopsy DNA: are in vitro strains representative of in vivo strains. Eur J Gastroenterol Hepatol. 1998;10:683-687.  [PubMed]  [DOI]
30.  Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, Rappuoli R, Covacci A. cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci USA. 1996;93:14648-14653.  [PubMed]  [DOI]
31.  Parsonnet J, Friedman GD, Orentreich N, Vogelman H. Risk for gastric cancer in people with CagA positive or CagA negative Helicobacter pylori infection. Gut. 1997;40:297-301.  [PubMed]  [DOI]
32.  Mitchell HM, Hazell SL, Bohane TD, Hu P, Chen M, Li YY. The prevalence of antibody to CagA in children is not a marker for specific disease. J Pediatr Gastroenterol Nutr. 1999;28:71-75.  [PubMed]  [DOI]
33.  Beales IL, Crabtree JE, Scunes D, Covacci A, Calam J. Antibodies to CagA protein are associated with gastric atrophy in Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 1996;8:645-649.  [PubMed]  [DOI]
34.  Loeb M, Jayaratne P, Jones N, Sihoe A, Sherman P. Lack of correlation between vacuolating cytotoxin activity, cagA gene in Helicobacter pylori, and peptic ulcer disease in children. Eur J Clin Microbiol Infect Dis. 1998;17:653-656.  [PubMed]  [DOI]
35.  Celik J, Su B, Tirén U, Finkel Y, Thoresson AC, Engstrand L, Sandstedt B, Bernander S, Normark S. Virulence and colonization-associated properties of Helicobacter pylori isolated from children and adolescents. J Infect Dis. 1998;177:247-252.  [PubMed]  [DOI]
36.  Corthésy-Theulaz I, Porta N, Pringault E, Racine L, Bogdanova A, Kraehenbuhl JP, Blum AL, Michetti P. Adhesion of Helicobacter pylori to polarized T84 human intestinal cell monolayers is pH dependent. Infect Immun. 1996;64:3827-3832.  [PubMed]  [DOI]
37.  Alkout AM, Blackwell CC, Weir DM, Poxton IR, Elton RA, Luman W, Palmer K. Isolation of a cell surface component of Helicobacter pylori that binds H type 2, Lewis(a), and Lewis(b) antigens. Gastroenterology. 1997;112:1179-1187.  [PubMed]  [DOI]
38.  Kirkland T, Viriyakosol S, Perez-Perez GI, Blaser MJ. Helicobacter pylori lipopolysaccharide can activate 70Z/3 cells via CD14. Infect Immun. 1997;65:604-608.  [PubMed]  [DOI]
39.  Appelmelk BJ, Negrini R, Moran AP, Kuipers EJ. Molecular mimicry between Helicobacter pylori and the host. Trends Microbiol. 1997;5:70-73.  [PubMed]  [DOI]
40.  Negrini R, Savio A, Poiesi C, Appelmelk BJ, Buffoli F, Paterlini A, Cesari P, Graffeo M, Vaira D, Franzin G. Antigenic mimicry between Helicobacter pylori and gastric mucosa in the pathogenesis of body atrophic gastritis. Gastroenterology. 1996;111:655-665.  [PubMed]  [DOI]
41.  Valle J, Sipponen P, Pajares JM. Geographical variations in Helicobacter pylori gastritis and gastric cancer. Cur Opin Gastroenterol. 1997;13:35-39.  [PubMed]  [DOI]
42.  Piotrowski J, Piotrowski E, Skrodzka D, Slomiany A, Slomiany BL. Induction of acute gastritis and epithelial apoptosis by Helicobacter pylori lipopolysaccharide. Scand J Gastroenterol. 1997;32:203-211.  [PubMed]  [DOI]
43.  Solcia E, Fiocca R, Luinetti O, Villani L, Padovan L, Calistri D, Ranzani GN, Chiaravalli A, Capella C. Intestinal and diffuse gastric cancers arise in a different background of Helicobacter pylori gastritis through different gene involvement. Am J Surg Pathol. 1996;20 Suppl 1:S8-22.  [PubMed]  [DOI]
44.  Bode G, Rothenbacher D, Brenner H, Adler G. Helicobacter pylori and abdominal symptoms: a population-based study among preschool children in southern Germany. Pediatrics. 1998;101:634-637.  [PubMed]  [DOI]
45.  Reifen R, Rasooly I, Drumm B, Murphy K, Sherman P. Helicobacter pylori infection in children. Is there specific symptomatology. Dig Dis Sci. 1994;39:1488-1492.  [PubMed]  [DOI]
46.  Gormally SM, Prakash N, Durnin MT, Daly LE, Clyne M, Kierce BM, Drumm B. Association of symptoms with Helicobacter pylori infection in children. J Pediatr. 1995;126:753-756.  [PubMed]  [DOI]
47.  Blecker U, Hauser B, Lanciers S, Keymolen K, Vandenplas Y. Symptomatology of Helicobacter pylori infection in children. Acta Paediatr. 1996;85:1156-1158.  [PubMed]  [DOI]
48.  Rowland M, Drumm B. Clinical significance of Helicobacter infection in children. Br Med Bull. 1998;54:95-103.  [PubMed]  [DOI]
49.  Wewer V, Andersen LP, Paerregaard A, Gernow AB, Hart Hansen JP, Matzen P, Krasilnikoff PA. The prevalence and related symptomatology of Helicobacter pylori in children with recurrent abdominal pain. Acta Paediatr. 1998;87:830-835.  [PubMed]  [DOI]
50.  Hardikar W, Feekery C, Smith A, Oberklaid F, Grimwood K. Helicobacter pylori and recurrent abdominal pain in children. J Pediatr Gastroenterol Nutr. 1996;22:148-152.  [PubMed]  [DOI]
51.  Günel E, Findik D, Cağlayan O, Cağlayan F, Topgaç Z. Helicobacter pylori and hypergastrinemia in children with recurrent abdominal pain. Pediatr Surg Int. 1998;14:40-42.  [PubMed]  [DOI]
52.  Camorlinga-Ponce M, Torres J, Perez-Perez G, Leal-Herrera Y, Gonzalez-Ortiz B, Madrazo de la Garza A, Gomez A, Muñoz O. Validation of a serologic test for the diagnosis of Helicobacter pylori infection and the immune response to urease and CagA in children. Am J Gastroenterol. 1998;93:1264-1270.  [PubMed]  [DOI]
53.  Armstrong D. Helicobacter pylori infection and dyspepsia. Scand J Gastroenterol Suppl. 1996;215:38-47.  [PubMed]  [DOI]
54.  Werdmuller BF, Loffeld RJ. Helicobacter pylori infection has no role in the pathogenesis of reflux esophagitis. Dig Dis Sci. 1997;42:103-105.  [PubMed]  [DOI]
55.  Maconi G, Lazzaroni M, Sangaletti O, Bargiggia S, Vago L, Bianchi Porro G. Effect of Helicobacter pylori eradication on gastric histology, serum gastrin and pepsinogen I levels, and gastric emptying in patients with gastric ulcer. Am J Gastroenterol. 1997;92:1844-1848.  [PubMed]  [DOI]
56.  Fock KM, Khoo TK, Chia KS, Sim CS. Helicobacter pylori infection and gastric emptying of indigestible solids in patients with dysmotility-like dyspepsia. Scand J Gastroenterol. 1997;32:676-680.  [PubMed]  [DOI]
57.  Chang CS, Chen GH, Kao CH, Wang SJ, Peng SN, Huang CK. The effect of Helicobacter pylori infection on gastric emptying of digestible and indigestible solids in patients with nonulcer dyspepsia. Am J Gastroenterol. 1996;91:474-479.  [PubMed]  [DOI]
58.  Ilboudo D, Bougouma A, Sombie R, Sawadogo A, Sanou I, Diomande I. [Helicobacter pylori infections in children in the tropical zone. Endoscopic and histological aspects]. Gastroenterol Clin Biol. 1998;22:855-857.  [PubMed]  [DOI]
59.  Patel P, Mendall MA, Khulusi S, Northfield TC, Strachan DP. Helicobacter pylori infection in childhood: risk factors and effect on growth. BMJ. 1994;309:1119-1123.  [PubMed]  [DOI]
60.  Raymond J, Bergeret M, Benhamou PH, Mensah K, Dupont C. A 2-year study of Helicobacter pylori in children. J Clin Microbiol. 1994;32:461-463.  [PubMed]  [DOI]
61.  Perri F, Pastore M, Leandro G, Clemente R, Ghoos Y, Peeters M, Annese V, Quitadamo M, Latiano A, Rutgeerts P. Helicobacter pylori infection and growth delay in older children. Arch Dis Child. 1997;77:46-49.  [PubMed]  [DOI]
62.  Dale A, Thomas JE, Darboe MK, Coward WA, Harding M, Weaver LT. Helicobacter pylori infection, gastric acid secretion, and infant growth. J Pediatr Gastroenterol Nutr. 1998;26:393-397.  [PubMed]  [DOI]
63.  Aggarwal A. Helicobacter pylori infection: a cause of growth delay in children. Indian Pediatr. 1998;35:191-192.  [PubMed]  [DOI]
64.  Vaira D, Menegatti M, Salardi S, Alì A, Altomare Stella F, Figura N, Landi F, Holton J, Farinelli S, Cuccaro V. Helicobacter pylori and diminished growth in children: is it simply a marker of deprivation. Ital J Gastroenterol Hepatol. 1998;30:129-133.  [PubMed]  [DOI]
65.  Farthing MJ. Helicobacter pylori infection: an overview. Br Med Bull. 1998;54:1-6.  [PubMed]  [DOI]
66.  Mendall MA, Patel P, Asante M, Ballam L, Morris J, Strachan DP, Camm AJ, Northfield TC. Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease. Heart. 1997;78:273-277.  [PubMed]  [DOI]
67.  Oderda G, Palli D, Saieva C, Chiorboli E, Bona G. Short stature and Helicobacter pylori infection in italian children: prospective multicentre hospital based case-control study. The Italian Study Group on Short Stature and H pylori. BMJ. 1998;317:514-515.  [PubMed]  [DOI]
68.  Isenbarger DW, Bodhidatta L, Hoge CW, Nirdnoy W, Pitarangsi C, Umpawasiri U, Echeverria P. Prospective study of the incidence of diarrheal disease and Helicobacter pylori infection among children in an orphanage in Thailand. Am J Trop Med Hyg. 1998;59:796-800.  [PubMed]  [DOI]
69.  Rosenstock SJ, Anderson LP, Bonevie O, Jorgensen T. Serum Lipids, body indices, age o menarche and Helicobacter pylori in-fection in 1756 Danish women. Gut. 1996;39:A62.  [PubMed]  [DOI]
70.  Pretolani S, Bonvicini F, Arienti V, Baldini L, Epidamio G, Stefameli ML, Giullianelli G, Cecofoeldi C, Glutomizi GC, Djihoud A. Late onset of menstrual cycle in H.pylori infected females in the general population. Int J Gastroenterol. 1996;28:200-201.  [PubMed]  [DOI]
71.  Blecker U, Hauser B, Vandenplas Y. "Hemoptysis" as an expression of Helicobacter pylori infection. J Pediatr Gastroenterol Nutr. 1994;18:116-117.  [PubMed]  [DOI]
72.  Barabino A, Dufour C, Marino CE, Claudiani F, De Alessandri A. Unexplained refractory iron-deficiency anemia associated with Helicobacter pylori gastric infection in children: further clinical evidence. J Pediatr Gastroenterol Nutr. 1999;28:116-119.  [PubMed]  [DOI]
73.  Whincup PH, Mendall MA, Perry IJ, Strachan DP, Walker M. Prospective relations between Helicobacter pylori infection, coronary heart disease, and stroke in middle aged men. Heart. 1996;75:568-572.  [PubMed]  [DOI]
74.  Gasbarrini A, Franceschi F, Gasbarrini G, Pola P. Extraintestinal pathology associated with Helicobacter infection. Eur J Gastroenterol Hepatol. 1997;9:231-233.  [PubMed]  [DOI]
75.  Figura N, Tabaqchali S. Bacterial pathogenic factors. Cur Opin Gastroenterol. 1996;12:33-36.  [PubMed]  [DOI]
76.  Kolibásová K, Tóthová I, Baumgartner J, Filo V. Eradication of Helicobacter pylori as the only successful treatment in rosacea. Arch Dermatol. 1996;132:1393.  [PubMed]  [DOI]
77.  Fox JG, Yan L, Shames B, Campbell J, Murphy JC, Li X. Persistent hepatitis and enterocolitis in germfree mice infected with Helicobacter hepaticus. Infect Immun. 1996;64:3673-3681.  [PubMed]  [DOI]
78.  Fox JG, Dewhirst FE, Shen Z, Feng Y, Taylor NS, Paster BJ, Ericson RL, Lau CN, Correa P, Araya JC. Hepatic Helicobacter species identified in bile and gallbladder tissue from Chileans with chronic cholecystitis. Gastroenterology. 1998;114:755-763.  [PubMed]  [DOI]
79.  Corrado G, Luzzi I, Lucarelli S, Frediani T, Pacchiarotti C, Cavaliere M, Rea P, Cardi E. Positive association between Helicobacter pylori infection and food allergy in children. Scand J Gastroenterol. 1998;33:1135-1139.  [PubMed]  [DOI]
80.  Gold BD, Khanna B, Huang LM, Lee CY, Banatvala N. Helicobacter pylori acquisition in infancy after decline of maternal passive immunity. Pediatr Res. 1997;41:641-646.  [PubMed]  [DOI]
81.  Rothenbacher D, Bode G, Berg G, Knayer U, Gonser T, Adler G, Brenner H. Helicobacter pylori among preschool children and their parents: evidence of parent-child transmission. J Infect Dis. 1999;179:398-402.  [PubMed]  [DOI]
82.  Thomas JE, Austin S, Dale A, McClean P, Harding M, Coward WA, Weaver LT. Protection by human milk IgA against Helicobacter pylori infection in infancy. Lancet. 1993;342:121.  [PubMed]  [DOI]
83.  Best LM, Veldhuyzen van Zanten SJ, Sherman PM, Bezanson GS. Serological detection of Helicobacter pylori antibodies in children and their parents. J Clin Microbiol. 1994;32:1193-1196.  [PubMed]  [DOI]
84.  Strömqvist M, Falk P, Bergström S, Hansson L, Lönnerdal B, Normark S, Hernell O. Human milk kappa-casein and inhibition of Helicobacter pylori adhesion to human gastric mucosa. J Pediatr Gastroenterol Nutr. 1995;21:288-296.  [PubMed]  [DOI]
85.  Crabtree JE, Mahony MJ, Taylor JD, Heatley RV, Littlewood JM, Tompkins DS. Immune responses to Helicobacter pylori in children with recurrent abdominal pain. J Clin Pathol. 1991;44:768-771.  [PubMed]  [DOI]
86.  Blecker U, Vandenplas Y. Usefulness of specific IgM in the diagnosis of Helicobacter pylori infection. Pediatrics. 1994;93:342-343.  [PubMed]  [DOI]
87.  Blecker U, Lanciers S, Keppens E, Vandenplas Y. Evolution of Helicobacter pylori positivity in infants born from positive mothers. J Pediatr Gastroenterol Nutr. 1994;19:87-90.  [PubMed]  [DOI]
88.  Blecker U, Lanciers S, Hauser B, Vandenplas Y. The prevalence of Helicobacter pylori positivity in a symptom-free population, aged 1 to 40 years. J Clin Epidemiol. 1994;47:1095-1098.  [PubMed]  [DOI]
89.  Rehnberg-Laiho L, Rautelin H, Valle M, Kosunen TU. Persisting Helicobacter antibodies in Finnish children and adolescents between two and twenty years of age. Pediatr Infect Dis J. 1998;17:796-799.  [PubMed]  [DOI]
90.  Rutigliano V, Ierardi E, Francavilla R, Castellaneta S, Margiotta M, Amoruso A, Marrazza E, Traversa A, Panella C, Rigillo N. Helicobacter pylori and nonulcer dyspepsia in childhood: clinical pattern, diagnostic techniques, and bacterial strains. J Pediatr Gastroenterol Nutr. 1999;28:296-300.  [PubMed]  [DOI]
91.  Lionetti P, Amarri S, Silenzi F, Galli L, Cellini M, de Martino M, Vierucci A. Prevalence of Helicobacter pylori infection detected by serology and 13C-urea breath test in HIV-1 perinatally infected children. J Pediatr Gastroenterol Nutr. 1999;28:301-306.  [PubMed]  [DOI]
92.  Blecker U, Keymolen K, Lanciers S, Bahwere P, Souayah H, Levy J, Vandenplas Y. The prevalence of Helicobacter pylori positivity in human immunodeficiency virus-infected children. J Pediatr Gastroenterol Nutr. 1994;19:417-420.  [PubMed]  [DOI]
93.  Mégraud F. Advantages and disadvantages of current diagnostic tests for the detection of Helicobacter pylori. Scand J Gastroenterol Suppl. 1996;215:57-62.  [PubMed]  [DOI]
94.  Malfertheiner P, Morain CO, Michetti P. The maastricht guidelines and other innovations. Cur Opin Gastroenterol. 1997;13:1-7.  [PubMed]  [DOI]
95.  Lee SG, Kim C, Ha YC. Successful cultivation of a potentially pathogenic coccoid organism with trophism for gastric mucin. Infect Immun. 1997;65:49-54.  [PubMed]  [DOI]
96.  Moran AP. Coccoid forms of Helicobacter pylori. Helicobacter. 1997;2:109-110.  [PubMed]  [DOI]
97.  Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20:1161-1181.  [PubMed]  [DOI]
98.  Laine L, Estrada R, Lewin DN, Cohen H. The influence of warming on rapid urease test results: a prospective evaluation. Gastrointest Endosc. 1996;44:429-432.  [PubMed]  [DOI]
99.  Elitsur Y, Hill I, Lichtman SN, Rosenberg AJ. Prospective comparison of rapid urease tests (PyloriTek, CLO test) for the diagnosis of Helicobacter pylori infection in symptomatic children: a pediatric multicenter study. Am J Gastroenterol. 1998;93:217-219.  [PubMed]  [DOI]
100.  Labenz J, Bärsch G, Peitz U, Aygen S, Hennemann O, Tillenburg B, Becker T, Stolte M. Validity of a novel biopsy urease test (HUT) and a simplified 13C-urea breath test for diagnosis of Helicobacter pylori infection and estimation of the severity of gastritis. Digestion. 1996;57:391-397.  [PubMed]  [DOI]
101.  Drumm B, Sherman P, Cutz E, Karmali M. Association of Campylobacter pylori on the gastric mucosa with antral gastritis in children. N Engl J Med. 1987;316:1557-1561.  [PubMed]  [DOI]
102.  Westblom TU. Molecular diagnosis of Helicobacter pylori. Immunol Invest. 1997;26:163-174.  [PubMed]  [DOI]
103.  Oksanen K, Kainulainen H, Ruuska T, Mäki M, Ashorn M. Reverse transcription-polymerase chain reaction in the diagnosis of Helicobacter pylori infection in Finnish children. J Pediatr Gastroenterol Nutr. 1999;28:252-256.  [PubMed]  [DOI]
104.  Furuta T, Kaneko E, Suzuki M, Arai H, Futami H. Quantitative study of Helicobacter pylori in gastric mucus by competitive PCR using synthetic DNA fragments. J Clin Microbiol. 1996;34:2421-2425.  [PubMed]  [DOI]
105.  Nilsson HO, Aleljung P, Nilsson I, Tysziewicz T, Wadstr-m T. Immunomagnetic bead enrichment and PCR for detection of Helicobacter pylori in human stools. J Microbiol Meth. 1996;27:73-79.  [PubMed]  [DOI]
106.  Casswall TH, Nilsson HO, Bergström M, Aleljung P, Wadström T, Dahlström AK, Albert MJ, Sarker SA. Evaluation of serology, 13C-urea breath test, and polymerase chain reaction of stool samples to detect Helicobacter pylori in Bangladeshi children. J Pediatr Gastroenterol Nutr. 1999;28:31-36.  [PubMed]  [DOI]
107.  Luzza F, Oderda G, Maletta M, Imeneo M, Mesuraca L, Chioboli E, Lerro P, Guandalini S, Pallone F. Salivary immunoglobulin G assay to diagnose Helicobacter pylori infection in children. J Clin Microbiol. 1997;35:3358-3360.  [PubMed]  [DOI]
108.  Christie JM, McNulty CA, Shepherd NA, Valori RM. Is saliva serology useful for the diagnosis of Helicobacter pylori. Gut. 1996;39:27-30.  [PubMed]  [DOI]
109.  Reilly TG, Poxon V, Sanders DS, Elliott TS, Walt RP. Comparison of serum, salivary, and rapid whole blood diagnostic tests for Helicobacter pylori and their validation against endoscopy based tests. Gut. 1997;40:454-458.  [PubMed]  [DOI]
110.  Blecker U, Lanciers S, Hauser B, Vandenplas Y. Diagnosis of Helicobacter pylori infection in adults and children by using the Malakit Helicobacter pylori, a commercially available enzyme-linked immunosorbent assay. J Clin Microbiol. 1993;31:1770-1773.  [PubMed]  [DOI]
111.  Thomas JE, Dale A, Harding M, Coward WA, Cole TJ, Weaver LT. Helicobacter pylori colonization in early life. Pediatr Res. 1999;45:218-223.  [PubMed]  [DOI]
112.  Loy CT, Irwig LM, Katelaris PH, Talley NJ. Do commercial serological kits for Helicobacter pylori infection differ in accuracy A meta-analysis. Am J Gastroenterol. 1996;91:1138-1144.  [PubMed]  [DOI]
113.  Duggan A, Logan R, Knifton A, Logan R. Accuracy of near-patient blood tests for Helicobacter pylori. Lancet. 1996;348:617.  [PubMed]  [DOI]
114.  Borody TJ, Andrews P, Shortis NP. Evaluation of whole blood antibody kit to detect active Helicobacter pylori infection. Am J Gastroenterol. 1996;91:2509-2512.  [PubMed]  [DOI]
115.  Cutler AF, Prasad VM. Long-term follow-up of Helicobacter pylori serology after successful eradication. Am J Gastroenterol. 1996;91:85-88.  [PubMed]  [DOI]
116.  Blecker U, Lanciers S, Hauser B, de Pont SM, Vandenplas Y. The contribution of specific immunoglobulin M antibodies to the diagnosis of Helicobacter pylori infection in children. Eur J Gastroenterol Hepatol. 1995;7:979-983.  [PubMed]  [DOI]
117.  Martín-de-Argila C, Boixeda D, Cantón R, Valdezate S, Mir N, De Rafael L, Gisbert JP, Baquero F. Usefulness of the combined IgG and IgA antibody determinations for serodiagnosis of Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 1997;9:1191-1196.  [PubMed]  [DOI]
118.  Nilsson I, Ljungh A, Aleljung P, Wadström T. Immunoblot assay for serodiagnosis of Helicobacter pylori infections. J Clin Microbiol. 1997;35:427-432.  [PubMed]  [DOI]
119.  Domínguez-Muñoz JE, Leodolter A, Sauerbruch T, Malfertheiner P. A citric acid solution is an optimal test drink in the 13C-urea breath test for the diagnosis of Helicobacter pylori infection. Gut. 1997;40:459-462.  [PubMed]  [DOI]
120.  Rowland M, Lambert I, Gormally S, Daly LE, Thomas JE, Hetherington C, Durnin M, Drumm B. Carbon 13-labeled urea breath test for the diagnosis of Helicobacter pylori infection in children. J Pediatr. 1997;131:815-820.  [PubMed]  [DOI]
121.  Malaty HM, el-Zimaity HM, Genta RM, Klein PD, Graham DY. Twenty-minute fasting version of the US 13C-urea breath test for the diagnosis of H. pylori infection. Helicobacter. 1996;1:165-167.  [PubMed]  [DOI]
122.  Cadranel S, Corvaglia L, Bontems P, Deprez C, Glupczynski Y, Van Riet A, Keppens E. Detection of Helicobacter pylori infection in children with a standardized and simplified 13C-urea breath test. J Pediatr Gastroenterol Nutr. 1998;27:275-280.  [PubMed]  [DOI]
123.  Vandenplas Y, Blecker U, Devreker T, Keppens E, Nijs J, Cadranel S, Pipeleers-Marichal M, Goossens A, Lauwers S. Contribution of the 13C-urea breath test to the detection of Helicobacter pylori gastritis in children. Pediatrics. 1992;90:608-611.  [PubMed]  [DOI]
124.  Delvin EE, Brazier JL, Deslandres C, Alvarez F, Russo P, Seidman E. Accuracy of the [13C]-urea breath test in diagnosing Helicobacter pylori gastritis in pediatric patients. J Pediatr Gastroenterol Nutr. 1999;28:59-62.  [PubMed]  [DOI]
125.  Hilker E, Stoll R, Domschke W. Quantitative assessment of Helicobacter pylori(HP) colonization of the gastric mucosa by 13C-urea breath test. Gastroenterology. 1994;106:A93.  [PubMed]  [DOI]
126.  Koletzko S, Haisch M, Seeboth I, Braden B, Hengels K, Koletzko B, Hering P. Isotope-selective non-dispersive infrared spectrometry for detection of Helicobacter pylori infection with 13C-urea breath test. Lancet. 1995;345:961-962.  [PubMed]  [DOI]
127.  Atherton JC, Spiller RC. The urea breath test for Helicobacter pylori. Gut. 1994;35:723-725.  [PubMed]  [DOI]
128.  Bell DG. Clinical practice: breath tests. Br Med Bull. 1998;54:187-1 9 3.  [PubMed]  [DOI]
129.  Logan RP. Urea breath tests in the management of Helicobacter pylori infection. Gut. 1998;43 Suppl 1:S47-S50.  [PubMed]  [DOI]
130.  Parsonnet J. The incidence of Helicobacter pylori infection. Aliment Pharmacol Ther. 1995;9 Suppl 2:45-51.  [PubMed]  [DOI]
131.  Raymond J, Kalach N, Bergeret M, Sauve-Martin H, Benhamou P, Dupont C. [Prevalence of Helicobacter pylori infection in children according to their age. A retrospective study]. Arch Pediatr. 1998;5:617-620.  [PubMed]  [DOI]
132.  Malaty HM, Kim JG, Kim SD, Graham DY. Prevalence of Helicobacter pylori infection in Korean children: inverse relation to socioeconomic status despite a uniformly high prevalence in adults. Am J Epidemiol. 1996;143:257-262.  [PubMed]  [DOI]
133.  Neale KR, Logan RP. The epidemiology and transmission of Helicobacter pylori infection in children. Aliment Pharmacol Ther. 1995;9 Suppl 2:77-84.  [PubMed]  [DOI]
134.  Veldhuyzen van Zanten SJ, Pollak PT, Best LM, Bezanson GS, Marrie T. Increasing prevalence of Helicobacter pylori infection with age: continuous risk of infection in adults rather than cohort effect. J Infect Dis. 1994;169:434-437.  [PubMed]  [DOI]
135.  Perry F, Pastore M, Latiano A, Annese V, Clemente R, Quitadamo M, Caruso N, Villani MR, Andriulli A. H. pylori infection in childhood: a fluctuating disease with spontaneous eradications and recurrences. Ital J Gastroenterol. 1996;28:193.  [PubMed]  [DOI]
136.  Kumagai T, Malaty HM, Graham DY, Hosogaya S, Misawa K, Furihata K, Ota H, Sei C, Tanaka E, Akamatsu T. Acquisition versus loss of Helicobacter pylori infection in Japan: results from an 8-year birth cohort study. J Infect Dis. 1998;178:717-721.  [PubMed]  [DOI]
137.  Kuipers EJ, Peña AS, van Kamp G, Uyterlinde AM, Pals G, Pels NF, Kurz-Pohlmann E, Meuwissen SG. Seroconversion for Helicobacter pylori. Lancet. 1993;342:328-331.  [PubMed]  [DOI]
138.  Blecker U, Hauser B, Lanciers S, Peeters S, Suys B, Vandenplas Y. The prevalence of Helicobacter pylori-positive serology in asymptomatic children. J Pediatr Gastroenterol Nutr. 1993;16:252-256.  [PubMed]  [DOI]
139.  Kato S, Abukawa D, Furuyama N, Iinuma K. Helicobacter pylori reinfection rates in children after eradication therapy. J Pediatr Gastroenterol Nutr. 1998;27:543-546.  [PubMed]  [DOI]
140.  Bell GD, Powell KU. Helicobacter pylori reinfection after apparent eradication--the Ipswich experience. Scand J Gastroenterol Suppl. 1996;215:96-104.  [PubMed]  [DOI]
141.  Figueroa G, Acuña R, Troncoso M, Portell DP, Toledo MS, Albornoz V, Vigneaux J. Low H. pylori reinfection rate after triple therapy in Chilean duodenal ulcer patients. Am J Gastroenterol. 1996;91:1395-1399.  [PubMed]  [DOI]
142.  Figueroa G, Acuña R, Troncoso M, Portell DP, Toledo MS, Valenzuela J. Helicobacter pylori infection in Chile. Clin Infect Dis. 1997;25:983-989.  [PubMed]  [DOI]
143.  Huang FC, Chang MH, Hsu HY, Lee PI, Shun CT. Long-term follow-up of duodenal ulcer in children before and after eradication of Helicobacter pylori. J Pediatr Gastroenterol Nutr. 1999;28:76-80.  [PubMed]  [DOI]
144.  Schütze K, Hentschel E, Dragosics B, Hirschl AM. Helicobacter pylori reinfection with identical organisms: transmission by the patients' spouses. Gut. 1995;36:831-833.  [PubMed]  [DOI]
145.  Oderda G, Ponzetto A, Boero M, Bellis D, Forni M, Vaira D, Ansaldi N. Family treatment of symptomatic children with Helicobacter pylori infection. Ital J Gastroenterol Hepatol. 1997;29:509-514.  [PubMed]  [DOI]
146.  Marshall DG, Coleman DC, Sullivan DJ, Xia H, O'Moráin CA, Smyth CJ. Genomic DNA fingerprinting of clinical isolates of Helicobacter pylori using short oligonucleotide probes containing repetitive sequences. J Appl Bacteriol. 1996;81:509-517.  [PubMed]  [DOI]
147.  Axon AT. The transmission of Helicobacter pylori: which theory fits the facts. Eur J Gastroenterol Hepatol. 1996;8:1-2.  [PubMed]  [DOI]
148.  Cammarota G, Tursi A, Montalto M, Papa A, Veneto G, Bernardi S, Boari A, Colizzi V, Fedeli G, Gasbarrini G. Role of dental plaque in the transmission of Helicobacter pylori infection. J Clin Gastroenterol. 1996;22:174-177.  [PubMed]  [DOI]
149.  Ma JL, You WC, Gail MH, Zhang L, Blot WJ, Chang YS, Jiang J, Liu WD, Hu YR, Brown LM. Helicobacter pylori infection and mode of transmission in a population at high risk of stomach cancer. Int J Epidemiol. 1998;27:570-573.  [PubMed]  [DOI]
150.  Grübel P, Hoffman JS, Chong FK, Burstein NA, Mepani C, Cave DR. Vector potential of houseflies (Musca domestica) for Helicobacter pylori. J Clin Microbiol. 1997;35:1300-1303.  [PubMed]  [DOI]
151.  Bode G, Rothenbacher D, Brenner H, Adler G. Pets are not a risk factor for Helicobacter pylori infection in young children: results of a population-based study in Southern Germany. Pediatr Infect Dis J. 1998;17:909-912.  [PubMed]  [DOI]
152.  Figura N. Mouth-to-mouth resuscitation and Helicobacter pylori infection. Lancet. 1996;347:1342.  [PubMed]  [DOI]
153.  Segal ED, Falkow S, Tompkins LS. Helicobacter pylori attachment to gastric cells induces cytoskeletal rearrangements and tyrosine phosphorylation of host cell proteins. Proc Natl Acad Sci USA. 1996;93:1259-1264.  [PubMed]  [DOI]
154.  Wadström T, Hirmo S, Nilsson B. Biochemical aspects of H. pylori adhesion. J Physiol Pharmacol. 1997;48:325-331.  [PubMed]  [DOI]
155.  Hulten K, Han SW, Enroth H, Klein PD, Opekun AR, Gilman RH, Evans DG, Engstrand L, Graham DY, El-Zaatari FA. Helicobacter pylori in the drinking water in Peru. Gastroenterology. 1996;110:1031-1035.  [PubMed]  [DOI]
156.  NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease. JAMA. 1994;272:65-69.  [PubMed]  [DOI]
157.  Labenz J, Blum AL, Bayerdörffer E, Meining A, Stolte M, Börsch G. Curing Helicobacter pylori infection in patients with duodenal ulcer may provoke reflux esophagitis. Gastroenterology. 1997;112:1442-1447.  [PubMed]  [DOI]
158.  Beales IL, Calam J. Effect of N alpha-methyl-histamine on acid secretion in isolated cultured rabbit parietal cells: implications for Helicobacter pylori associated gastritis and gastric physiology. Gut. 1997;40:14-19.  [PubMed]  [DOI]
159.  Appelmelk BJ, Simoons-Smit I, Negrini R, Moran AP, Aspinall GO, Forte JG, De Vries T, Quan H, Verboom T, Maaskant JJ. Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity. Infect Immun. 1996;64:2031-2040.  [PubMed]  [DOI]
160.  The European Helicobacter pylori Study Group. Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. European Helicobacter Pylori Study Group. Gut. 1997;41:8-13.  [PubMed]  [DOI]
161.  Lee J, O'Morain C. Consensus or confusion: a review of existing national guidelines on Helicobacter pylori-related disease. Eur J Gastroenterol Hepatol. 1997;9:527-531.  [PubMed]  [DOI]
162.  Sherman PM, Hunt RH. Why guidelines are required for the treatment of Helicobacter pylori infection in children. Clin Invest Med. 1996;19:362-367.  [PubMed]  [DOI]
163.  van Zwet AA, Vandenbroucke-Grauls CM, Thijs JC, van der Wouden EJ, Gerrits MM, Kusters JG. Stable amoxicillin resistance in Helicobacter pylori. Lancet. 1998;352:1595.  [PubMed]  [DOI]
164.  Raymond J, Kalach N, Bergeret M, Benhamou PH, Barbet JP, Gendrel D, Dupont C. Effect of metronidazole resistance on bacterial eradication of Helicobacter pylori in infected children. Antimicrob Agents Chemother. 1998;42:1334-1335.  [PubMed]  [DOI]
165.  Tirén U, Sandstedt B, Finkel Y. Helicobacter pylori gastritis in children: efficacy of 2 weeks of treatment with clarithromycin, amoxicillin and omeprazole. Acta Paediatr. 1999;88:166-168.  [PubMed]  [DOI]
166.  Kato S, Ritsuno H, Ohnuma K, Iinuma K, Sugiyama T, Asaka M. Safety and efficacy of one-week triple therapy for eradicating Helicobacter pylori in children. Helicobacter. 1998;3:278-282.  [PubMed]  [DOI]
167.  Casswall TH, Alfvén G, Drapinski M, Bergström M, Dahlström KA. One-week treatment with omeprazole, clarithromycin, and metronidazole in children with Helicobacter pylori infection. J Pediatr Gastroenterol Nutr. 1998;27:415-418.  [PubMed]  [DOI]
168.  Moshkowitz M, Reif S, Brill S, Ringel Y, Arber N, Halpern Z, Bujanover Y. One-week triple therapy with omeprazole, clarithromycin, and nitroimidazole for Helicobacter pylori infection in children and adolescents. Pediatrics. 1998;102:e14.  [PubMed]  [DOI]
169.  Kato S, Takeyama J, Ebina K, Naganuma H. Omeprazole-based dual and triple regimens for Helicobacter pylori eradication in children. Pediatrics. 1997;100:E3.  [PubMed]  [DOI]
170.  van der Hulst RW, Keller JJ, Rauws EA, Tytgat GN. Treatment of Helicobacter pylori infection: a review of the world literature. Helicobacter. 1996;1:6-19.  [PubMed]  [DOI]
171.  Oderda G. Management of Helicobacter pylori infection in children. Gut. 1998;43 Suppl 1:S10-S13.  [PubMed]  [DOI]
172.  Patel P, Khulusi S, Mendall MA, Lloyd R, Jazrawi R, Maxwell JD, Northfield TC. Prospective screening of dyspeptic patients by Helicobacter pylori serology. Lancet. 1995;346:1315-1318.  [PubMed]  [DOI]
173.  Vakil N, Ashorn M. Cost-effectiveness of noninvasive testing and treatment strategies for H. pylori infection in children with dyspepsia. Am J Gastroenterol. 1998;93:562-568.  [PubMed]  [DOI]
174.  Jones NL, Bourke B, Sherman PM. Breath testing for Helicobacter pylori infection in children: a breath of fresh air. J Pediatr. 1997;131:791-793.  [PubMed]  [DOI]
175.  Verdú EF, Armstrong D, Idström JP, Labenz J, Stolte M, Börsch G, Blum AL. Intragastric pH during treatment with omeprazole: role of Helicobacter pylori and H. pylori-associated gastritis. Scand J Gastroenterol. 1996;31:1151-1156.  [PubMed]  [DOI]
176.  Labenz J, Tillenburg B, Peitz U, Idström JP, Verdú EF, Stolte M, Börsch G, Blum AL. Helicobacter pylori augments the pH-increasing effect of omeprazole in patients with duodenal ulcer. Gastroenterology. 1996;110:725-732.  [PubMed]  [DOI]
177.  Eissele R, Brunner G, Simon B, Solcia E, Arnold R. Gastric mucosa during treatment with lansoprazole: Helicobacter pylori is a risk factor for argyrophil cell hyperplasia. Gastroenterology. 1997;112:707-717.  [PubMed]  [DOI]
178.  Kuipers EJ, Lundell L, Klinkenberg-Knol EC, Havu N, Festen HP, Liedman B, Lamers CB, Jansen JB, Dalenback J, Snel P. Atrophic gastritis and Helicobacter pylori infection in patients with reflux esophagitis treated with omeprazole or fundoplication. N Engl J Med. 1996;334:1018-1022.  [PubMed]  [DOI]
179.  Kosunen TU, Seppälä K, Sarna S, Sipponen P. Diagnostic value of decreasing IgG, IgA, and IgM antibody titres after eradication of Helicobacter pylori. Lancet. 1992;339:893-895.  [PubMed]  [DOI]
180.  Moshkowitz M, Konikoff FM, Peled Y, Santo M, Hallak A, Bujanover Y, Tiomny E, Gilat T. High Helicobacter pylori numbers are associated with low eradication rate after triple therapy. Gut. 1995;36:845-847.  [PubMed]  [DOI]
181.  Hughes NJ, Chalk PA, Clayton CL, Kelly DJ. Identification of carboxylation enzymes and characterization of a novel four-subunit pyruvate: flavodoxin oxidoreductase from Helicobacter pylori. J Bacteriol. 1995;177:3953-3959.  [PubMed]  [DOI]
182.  Kreiss C, Buclin T, Cosma M, Corthésy-Theulaz I, Michetti P. Safety of oral immunisation with recombinant urease in patients with Helicobacter pylori infection. Lancet. 1996;347:1630-1631.  [PubMed]  [DOI]
183.  Michetti P, Kreiss C, Kotloff KL, Porta N, Blanco JL, Bachmann D, Herranz M, Saldinger PF, Corthésy-Theulaz I, Losonsky G. Oral immunization with urease and Escherichia coli heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori-infected adults. Gastroenterology. 1999;116:804-812.  [PubMed]  [DOI]
184.  Mohammadi M, Czinn S, Redline R, Nedrud J. Adoptive transfer of Helicobacter specific Th1 or Th2 cells exacerbates Helicobacter associated gastritis, but only Th2 cells reduce the magnitude of infection. Gut. 1996;39:A45.  [PubMed]  [DOI]
185.  Mohammadi M, Czinn S, Redline R, Nedrud J. Helicobacter-specific cell-mediated immune responses display a predominant Th1 phenotype and promote a delayed-type hypersensitivity response in the stomachs of mice. J Immunol. 1996;156:4729-4738.  [PubMed]  [DOI]
186.  Saldinger PF, Porta N, Waanders GA, Launois P, Louis JA, Michetti P, Blum AL, Corthésy-Theulaz I. Therapeutic immunization against Helicobacter infected BALB/c mice induces a switch of the cellular response from Th1 to Th2. Gastroenterology. 1997;11:A108.  [PubMed]  [DOI]