Accelerated decline in Helicobacter pylori seroprevalence rate during the screen and treat project in Vammala, Finland, as demonstrated in 29- to 45-year-old pregnant women

The potential preventability of serious helicobacter-associated diseases - especially gastric cancer - has evoked interest in eradicating this pathogen from the population. We assessed the efficacy of the pioneering screen and treat intervention project in Vammala by studying helicobacter seroprevalence in pregnant women representing the normal population. Consecutive maternity clinic samples from native Finnish females at five different localities in 1995 (n=701) and 2000 (n=772) were investigated for class IgG H. pylori antibodies by enzyme immunoassay (Pyloriset EIA-G III, Orion Diagnostica, Espoo, Finland). In Vammala the change in helicobacter seroprevalence was -13%-units (between 1995 and 2000; p=0.0125, chi-square test) in > or =29-year-old females, +1.6%-units (difference statistically non-significant) in <29-year-old females, and -5.5%-units (difference statistically non-significant) in the whole study population. In the four reference localities studied, all the corresponding changes remained statistically non-significant. Thus, in Vammala the programme applied accelerated the decline of helicobacter infections in 29- to 45-year-old females and in 2000 the seroprevalence rate had also become significantly lower than that of the four reference communities combined (7.6% versus 13.5%, respectively, p=0.0433, chi-square test). The final outcome of the intervention project, i.e. the long-term effect of this decline on gastric cancer and peptic ulcer disease, remains to be evaluated.     

Helicobacter pylori infection in patients with selective immunoglobulin a deficiency

Selective immunoglobulin A (IgA) deficiency (IgAD) is the most common primary immunodeficiency in the western world. The aim of the study was to investigate the prevalence and clinical characteristics of Helicobacter pylori‐infected dyspeptic patients with IgAD. Case samples were drawn from all subjects ≥ 12 years of age (n = 104729) who had undergone serum total IgA measurements during 2004–14 for any reason at Leumit Healthcare Services (Israel) and had serum total IgA < 0·07 g/l. The control group was comprised of a random sample of remaining patients with a case–control ratio of 10 controls for each case. The dyspeptic diseases were identified and retrieved from Leumit Health Care Services electronic database using specific ICD‐9‐CM diagnostic codes. The case group included 347 subjects and the control group 3470 subjects. There were no significant differences in the prevalence of patients with dyspepsia [84 (24·2%) versus 821 (23·6%) for cases and controls, respectively]. Additionally, there was no difference in a proportion of dyspeptic H. pylori‐positive subjects [59 (17·1%) versus 524 (15·1%)] between the case and control groups. Only 59 (17%) among the 347 IgAD patients underwent gastroscopy. A significantly larger proportion of case subjects experienced several forms of gastritis [13 (61·9%) versus 38 (21·6%), P < 0·001), duodenal ulcers [seven (33·3%) versus 19 (10·8%); P = 0·01] and nodular lymphoid hyperplasia (NLH) [two (9·5%) versus none; P = 0·011]. IgAD is not associated with increased prevalence of H. pylori‐associated dyspepsia; nevertheless, H. pylori‐infected dyspeptic IgAD subjects experience more EGD‐proved gastritis, duodenal ulcers and NLH.     

幽门螺杆菌免疫奶羊的应答性实验研究

目的　以Hp全菌抗原免疫奶羊 ,观察羊奶中特异性抗体产生规律。方法　采用 6× 10 9CFU mLHp全菌抗原 ,通过滴鼻、多点皮下注射、妊娠期肌肉注射 3种途径免疫 3只产奶山羊。前两组于 0、14、2 1、2 8d接受 4次免疫接种 ,妊娠组于分娩前后 1个月每隔两周注射 1次。收集血清、乳清 ,以酶联免疫吸附试验进行样本中的IgA、IgG抗体测定。结果　 3种途径免疫奶羊后都激发了奶羊的系统免疫 ,使血清中IgG较免疫前都有很大升高 ;羊奶中IgA抗体水平滴鼻组 >妊娠组 >皮下组 ,IgG抗体水平妊娠组 >皮下组 >滴鼻组。结论　 3种途径都能激发奶羊机体的免疫应答 ,尤其是滴鼻免疫能够诱导机体同时产生不同部位的粘膜免疫和系统免疫 ,是一种敏感、安全、可行有效的免疫途径     

Non-invasive techniques for the diagnosis of Helicobacter pylori infection

Helicobacter pylori infection can be diagnosed by invasive techniques requiring endoscopy and biopsy (histologic examination, culture, polymerase chain reaction), and non-invasive techniques (serology, urea breath test, urine or blood, detection of H. pylori antigen in stool specimen). However, recent studies have demonstrated that a strategy of 'testing and treating' for H. pylori in uninvestigated, young (<50 years), dyspeptic patients in primary care is safe and reduces the need for endoscopy. Indeed, a number of clinical guidelines recommend non-invasive testing in dyspeptic patients followed by treatment of H. pylori in primary care based on clinical and economic analyses. Several non-invasive tests are currently available on the market. The choice depends on the clinical circumstances, the likelihood ratio of positive and negative tests, the cost-effectiveness of the testing strategy, and, finally, the availability of the tests. Nevertheless, two non-invasive tests are commonly used: the urea breath test, and the stool antigen test.     

Detection of Helicobacter pylori infection in symptomatic Bulgarian adults

This study assessed the prevalence of Helicobacter pylori in symptomatic Bulgarian adults by means of culture, Gram's stain and an in-house rapid urease test (RUT), and also assessed the H. pylori density by culture. In total, 1441 non-treated and 270 treated patients were evaluated. Most non-treated patients with ulcers (87.7%), gastric malignancy (79.2%) and other gastroduodenal diseases (73.4%) were H. pylori-positive. Among non-treated and treated patients, 75.3% and 54.8%, respectively, of elderly patients, and 78.3% and 56.1%, respectively, of other adults were H. pylori-positive. Two (0.1%) non-treated adults were Helicobacter heilmannii-positive. The accuracy of direct Gram's stain and the in-house RUT were 74.8% and 64.2% in non-treated patients, and 73.7% and 63.0% in treated patients, respectively. Culture was highly accurate (>95%) in both groups. Older age decreased the sensitivity of the RUT in non-treated patients by 10.7% and that of all tests in treated patients by 6.9-8.1%. Incubation for 11 days was required for the growth of 2% and 4% of the strains from treated patients on selective and non-selective medium, respectively. There were no differences in isolation rates between positive fresh (74.2%) and frozen (75.2%) specimens. In non-treated adults, a high H. pylori density (growth in all quadrants of the plates) was more common (43.1%) in ulcer patients than in other patients (25.4%). In conclusion, H. pylori infection was common in Bulgarian patients, and at a high density in >40% of ulcer patients, while H. heilmannii infection was uncommon. Culture provided a highly accurate diagnostic approach. Stomach biopsies from non-treated patients can be frozen for several days. The benefit of reporting H. pylori density, as determined by culture, requires further evaluation.     

胃粘膜局部抗幽门螺杆菌抗体IgA的研究

采用胃粘膜体外培养技术和免疫印迹技术研究了５１例慢性胃炎和消化性溃疡患者胃粘膜局部抗幽门螺杆菌（Ｈｐ）抗体ＩｇＡ，同时对其中１０例Ｈｐ阳性患者的血清ＩｇＡ作了分析。结果表明：４０例Ｈｐ阳性患者除１例外，其粘膜抗ＨｐＩｇＡ抗体均为阳性；１１例Ｈｐ阴性患者中，２例胃粘膜局部ＩｇＡ阳性，９例为阴性。该方法与常规方法检测Ｈｐ的符合率为９２．２％。粘膜局部ＩｇＡ识别５条左右条带，且识别条带具多样性。１０例Ｈｐ阳性且局部ＩｇＡ阳性患者的血清ＩｇＡ亦为阳性，但血清ＩｇＡ的识别条带较局部ＩｇＡ少，且染色浅，说明抗ＨｇＩｇＡ抗体以局部为主，该局部ＩｇＡ的作用值得进一步研究。     

Advantage of using a home-made ELISA kit for detection of Helicobacter pylori infection over commercially imported kits

PURPOSE: To evaluate a home-made ELISA kit for detection of Helicobacter pylori (Hp) infection and comparison of its immunologic criteria with those of foreign commercial kits. METHODS: A home-made IgG ELISA kit was developed using soluble antigenic fractions of Hp proteins. Confirmed sera were tested and serological criteria were evaluated through assessment of 199 serum samples. RESULTS: The accuracy, sensitivity and specificity values of home-made kit were 92, 92 and 90.4%, respectively. These immunologic criteria for Trinity kit were 95.2, 95.2 and 95% in comparison with IBL kit (91.3, 92.2 and 88.5%), BIOHIT kit (72.4, 41.6 and 94.1%) and HelicoBlot2.1 (94.2, 93.4 and 100%). Kappa agreement assessment demonstrated that two of the imported ELISA kits had fair to moderate agreement with the home-made kit while the other one had a poor agreement value. CONCLUSIONS: Apart from comparable values between the home-made kit and the most efficient imported kit (Trinity) there was significant cost benefit. Therefore, we recommend the home-made kit as a suitable substitution for detection of Hp infection in the Iranian population.     

Pathogenicity of Helicobacter pylori infection

Numerous Helicobacter pylori virulence factors, including various enzymes (urease, catalase, lipase, phospholipase and proteases), vacuolating cytotoxin (a product of expression of the vacA gene), and the immunogenic protein CagA, encoded by the cagA gene localised in the H. pylori pathogenicity island, are involved in the pathomechanism of infection caused by these organisms. This review presents the current state of knowledge concerning the molecular mechanisms and epidemiology of H. pylori infection, based on the published literature and recent unpublished observations.     

幽门螺杆菌感染对人牙龈组织细胞凋亡的影响

目的:观察正常牙龈组织中幽门螺杆菌(Hp)的感染情况及其对人牙龈组织细胞凋亡的影响。方法:采用聚合酶链式反应(PCR)检测30例健康牙龈组织中Hp感染情况,应用脱氧核糖核苷酸末端转移酶介导的原位缺口末端标记(TUNEL)法检测牙龈组织中的细胞凋亡指数,分析Hp对牙龈组织的毒性作用。结果:PCR检测的30名患者,Hp阳性率为40%。在TUNEL结果中,可见Hp阳性组有大量棕色凋亡细胞,部分细胞核固缩成团或核膜周围边集成环状。而正常对照组中阳性凋亡细胞较Hp感染组明显偏低,2组细胞凋亡指数差异有统计学意义。结论:Hp感染可能是引起牙龈组织细胞凋亡的因素之一。     

Correlations between the CagA Antigen and Serum Levels of Anti-Helicobacter pylori IgG and IgA in Children

We tested correlations between anti-Helicobacter pylori IgG and IgA levels and the urease test, anti-CagA protein antibody, degree of gastritis, and age. In total, 509 children (0–15 years) were enrolled. Subjects were stratified as 0–4 years (n = 132), 5–9 years (n = 274), and 10–15 years (n = 103) and subjected to the urease test, histopathology, ELISA, and western blot using whole-cell lysates of H. pylori strain 51. The positivity rate in the urease test (P = 0.003), the degree of chronic gastritis (P = 0.021), and H. pylori infiltration (P < 0.001) increased with age. The median titer for anti-H. pylori IgG was 732.5 IU/mL at 0–4 years, 689.0 IU/mL at 5–9 years, and 966.0 IU/mL at 10–15 years (P < 0.001); the median titer for anti-H. pylori IgA was 61.0 IU/mL at 0–4 years, 63.5 IU/mL at 5–9 years, and 75.0 IU/mL at 10–15 years (P < 0.001). The CagA-positivity rate was 26.5% at 0–4 years, 36.5% at 5–9 years, and 46.6% at 10–15 years for IgG (P = 0.036), and 11.3% at 0–4 years, 18.6% at 5–9 years, and 23.3% at 10–15 years for IgA (P < 0.001). Anti-H. pylori IgG and IgA titers increased with the urease test grade, chronic gastritis degree, active gastritis, and H. pylori infiltration. Presence of CagA-positivity is well correlated with a high urease test grade and high anti-H. pylori IgG/IgA levels.     

IgG subclass response to Helicobacter pylori and CagA antigens in children

Specific serum IgG subclass antibodies against Helicobacter pylori antigens and recombinant CagA were analysed in 75 symptomatic children with histologically confirmed H. pylori infection. H. pylori stimulated an IgG1 predominant response, and IgG3 titres showed a positive association with peptic ulcer disease, chronicity of antral inflammation and density of H. pylori colonization. Two methods used for assessing serum IgG CagA antibody status, i.e. Western blotting and enzyme-linked immunosorbent assay (ELISA), were concordant. CagA stimulated an IgG1 and IgG3 predominant humoral response. Total CagA IgG titres were higher in children with active and more severe chronic antral inflammation. These findings suggest that in children the systemic humoral immune response to H. pylori infection may reflect gastroduodenal pathology.     

根除儿童口腔幽门螺杆菌预防胃内幽门螺杆菌感染的多中心研究

目的:探讨根除儿童口腔幽门螺杆菌（Hp）预防胃内Hp感染的可能性。方法:采用多中心前瞻随机研究,选取口腔Hp阳性但胃内Hp阴性的幼儿园儿童共计427例,随机分为使用“无幽梅”牙膏组与普通牙膏组,分别接受“无幽梅”牙膏和普通牙膏。疗程结束后,再次检测口腔Hp,将口腔Hp阳性及阴性患者各分为一组,1年后行C13呼气试验检查,分析两组患者胃内Hp感染情况。口腔Hp检测方法采用特异度及敏感度双高的套式PCR方法。结果:随访1年,口腔Hp阴性组胃内Hp感染率为0.51%,口腔Hp阳性组胃内Hp感染率为6.51%,两组统计差异具有显著性（P<0.01）。结论:儿童根除口腔Hp可以降低胃内Hp感染的发生。     

Colostrum IgA1 antibodies recognize antigens from Helicobacter pylori and prevent cytoskeletal changes in human epithelial cells

Helicobacter pylori is a Gram-negative bacterium found on the luminal surface of the gastric mucosa in at least 50% of the world's human population. The protective effect of breastfeeding against H. pylori infection has been extensively reported; however, the mechanisms behind this protection remain poorly understood. Human IgA from colostrum has reactivity against H. pylori antigens. Despite that IgA1 and IgA2 display structural and functional differences, their reactivity against H. pylori had not been previously determined. We attested titers and reactivity of human colostrum-IgA subclasses by ELISA, immunoblot, and flow cytometry. Colostrum samples from healthy mothers had higher titers of IgA; and IgA1 mostly recognized H. pylori antigens. Moreover, we found a correlation between IgA1 reactivity and their neutralizing effect determined by inhibition of cytoskeletal changes in AGS cells infected with H. pylori. In conclusion, colostrum-IgA reduces H. pylori infection of epithelial gastric cells, suggesting an important role in preventing the bacteria establishment during the first months of life. As a whole, these results suggest that IgA1 from human colostrum provides protection that may help in the development of the mucosal immune system of newborn children.     

Five month persistence of Helicobacter pylori infection in guinea pigs

Seven Dunkin-Hartley guinea pigs were infected with the Sydney strain of H. pylori (SS1). Gastric histopathology was evaluated and serum antibody response to H. pylori cell-surface proteins was analysed by enzyme immunoassay (EIA) and immunoblot. Tissue and faecal samples from five control animals were analysed for the presence of naturally occurring Helicobacter spp. infection by culture and Helicobacter genus-specific PCR. The H. pylori infection persisted for 5 months, in most animals accompanied by a histologically severe antral gastritis, exhibiting focal degeneration and necrosis of gastric crypt epithelium. Increased numbers of mitotic figures were observed in the gastric epithelium, indicating a regenerative process. Infected animals displayed specific antibodies towards H. pylori cell-surface proteins in immunoblot, whereas EIA was of dubious value creating false-positive results. Serum complement C3 and cholesterol levels appeared to be elevated in infected animals. Helicobacter spp. infection was not detected in the control animals. The persistent infection, accompanied by severe gastritis and a prominent serum antibody response, and the apparent absence of a natural Helicobacter spp. infection makes the guinea pig model useful in H. pylori research.     

幽门螺杆菌相关抗原及宿主免疫应答的研究进展

幽门螺杆菌与多种胃肠道疾病诸如慢性胃炎,胃肠溃疡,胃腺瘤及胃癌等密切相关的结论已得到证实,预防和治疗幽门螺杆菌感染是控制其广泛传播的有效途径,此项工作虽早已开始,但至今未找到可行的方案.近来对幽门螺杆菌相关毒素的研究越来越多,这可作为研究幽门螺杆菌菌苗的重要依据;幽门螺杆菌诱发的宿主免疫应答以TH1反应为主,幽门螺杆菌感染者可出现系统和局部的抗体反应,这些抗体反应对机体不具保护作用且自身抗体对宿主上皮细胞还可能带来不良影响,阐明宿主免疫应答的机制对预防和治疗幽门螺杆菌感染具特殊意义.因此,本文主要介绍了脲素酶、空泡细胞毒素、cag相关基因蛋白,中性粒细胞蛋白等几种毒素及宿主免疫应答的研究现状,并对幽门螺杆菌的研究前景进行综述.     

非酒精性脂肪性肝病与幽门螺杆菌感染的相关性

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)本质上是一种肝代谢性疾病,其发病机制复杂,目前尚未完全明确.目前各项资料显示幽门螺杆菌感染(Helicobacter pylori,Hp)与NAFLD的发生和发展有密切的关系,但也有研究得出了相反的结论.对于存在争议的部分至今尚未解决,但如证实Hp感染可作为NAFLD的一种独立危险因素存在,则对NAFLD发病预测以及治疗提供帮助,因此研究两者相关性的工作仍然具有临床意义.     

Helicobacter pylori infections in IgA deficiency: lack of role for the secretory immune system

During the last years considerable attention has been focused on the possibility of the development of an oral vaccine against Helicobacter pylori. However, Helicobacter infection is known to be life-long, despite a vigorous immune response, and the hypothesis that an increased local production of secretory IgA in the gastric mucosa, due to vaccination, should protect against the colonization of the bacterium may therefore be questioned. In this study, when comparing the seropositivity and titre against H. pylori in IgA-deficient patients and age-related normal blood donors, it appears that lack of secretory IgA does not seem to have any major influence on the prevalence of the infection, nor is it reflected in titres of specific IgG antibodies. These results may argue against a pivotal role for IgA in the defence against Helicobacter, and raise questions about current strategies for the development of an oral vaccine against H. pylori and may point to a need for alternative therapeutic strategies.     

Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis

Background. Only a few reported studies focus on the natural history and course of advanced and severe chronic atrophic gastritis. Methods. In this study we followed 47 men (mean age 62 years) with advanced (moderate or severe) Helicobacter pylori-positive atrophic corpus gastritis. Duration of endoscopic follow-up was 6 years and follow-up based on serum levels of pepsinogen I and antibodies to H. pylori covered a period of 10 years. None of the patients was treated for H. pylori infection prior to end of follow-up. Results. The median H. pylori antibody titre declined (IgG from 4000 to 1300; IgA from 200 to 50) in the study population, and 11 men (23%) converted to seronegative (p=0.0005, Fisher's exact test). There was a small but significant (p=0.0004, Page's test) declining trend in mean atrophy score of the corpus during follow-up (from 2.5 to 2.2). However, no significant changes were observed in grade of atrophy or intestinal metaplasia of the antral mucosa or in grade of intestinal metaplasia in the corpus. The mean SPGI level remained at the initial low level during the entire follow-up. Conclusions. H. pylori antibodies disappear spontaneously within 10 years in almost one fourth of patients with advanced atrophic corpus gastritis. The disappearance of H. pylori antibodies is accompanied by no or more than a mild improvement of the gastric mucosa.     

Evaluation of the effect of presence of blood in the stomach on endoscopic diagnostic tests for Helicobacter pylori infection

Introduction: Presence of blood in the stomach has been thought to affect the performance of diagnostic tests used in detecting Helicobacter pylori (H. pylori) in the stomach. This study evaluated the effect of blood on the efficacy of rapid urease test (RUT) and microscopic appearance of the biopsy after staining with Giemsa stain. Materials and Methods: Patients with bleeding oesophageal varices who met the inclusion criteria were tested for H. pylori by RUT and microscopic examination of the biopsy. A repeat endoscopy, RUT and histology were done one month following initial presentation. The performance of the diagnostic tests was evaluated with and without the presence of intraluminal blood. A combined result of the two tests, RUT and histology, carried out in presence or absence of blood for the diagnosis of H. pylori, when considered together was considered as the gold standard. Results: Thirty six patients included in the study were in the ages ranging between 15-60 years (mean age = 44.14 years ±2.1). The combination of tests at both visits showed 20/36 (55.6%) patients were positive for H. pylori. The decrease in H. pylori positivity in the presence of blood was significant for RUT (8.3% vs. 38.9%; P=0.005) and combined test (19.4% vs. 47.2%; P=0.02) but the decrease in positivity for histology (11.1% vs 30.6%) was not significant (P=0.08). In the presence of blood, the sensitivity of RUT, histology and combined tests were 15%, 20% and 35%, respectively. In the absence of blood, the sensitivity of RUT, histology and combination of tests was 70%, 55% and 85%, respectively. Conclusion: Blood in the stomach significantly decreased the sensitivity of RUT, histology and the combination of both. Negative results of these tests in acute upper gastro intestinal (GI) bleeding should therefore be interpreted carefully.