纤维胃镜检查与幽门螺杆菌交叉感染检测报告

对胃镜检查导致幽门螺杆菌（Ｈｐ）交叉感染的可能性进行调查。结果从清洗消毒后胃镜活检吸引管道及活检钳采样培养出Ｈｐ。老年慢性胃炎患者随胃镜检查次数增多，Ｈｐ阳性率增高；Ｈｐ阴性胃炎患者随胃镜随访次数增加，Ｈｐ阳性率增高；Ｈｐ转为阳性随访者的平均年龄大于随机抽查、年龄匹配的正常和慢性胃炎对照中Ｈｐ阳性者。提示，胃镜及附件灭菌不严可成为Ｈｐ交叉感染的一个潜在途径，老年人接受多次胃镜检查可增加感染的危险性     

中国幽门螺杆菌基因组多样性与种群结构分析

目的 了解中国幽门螺杆菌（Helicobacter pylori,HP）基因组特征及种群结构。方法 利用中国不同地域不同疾病分离的10株HP的基因组序列,并整合公共数据库中其他地域的HP基因组数据,通过比较基因组和生物信息学方法分析中国HP的基因组与种群结构特征。结果 中国HP核心基因为1 203个。菌株特异基因为19～32个,这些基因可能与中国HP在不同地域、不同疾病宿主中的适应性进化有关。基因组变异较大区域主要集中在编码限制修饰系统的基因和编码四型分泌系统的基因。基于核心基因组单核苷酸多态性（SNP）的种群分析确定中国菌株均属于hpEastAsia群,hspEAsia亚群,且不同地域菌株具有地域聚集性特点。在3株中国HP基因组序列中发现了前噬菌体序列,携带噬菌体组装所需的必要元件。结论 基于核心基因组SNP分析中国菌株均属于hpEastAsia群,hspEAsia亚群,且具有地域聚集性。为深入挖掘中国不同地域不同疾病相关HP的遗传特征及研究噬菌体在HP进化与致病中的作用奠定了基础。     

Helicobacter pylori and endoscopy

Helicobacter pylori is possibly the most common bacterial infection of humans and is now recognized as the most important acquired cause of peptic ulceration. Epidemiological evidence also recently implicated this bacterium in the pathogenesis of gastric cancer. The mechanism of spread of the organism, by either the faecal-oral or oral-oral route, raises the possibility of transmission of this organism from infected patients to hospital staff particularly those involved in endoscopy. The evidence for an increased risk to endoscopists is contradictory, varying from none to a five-fold increase. This review summarizes the evidence for mode of transmission and risk to hospital staff from this important bacterium.     

幽门螺旋杆菌药敏试验指导的治疗方案和新一线四联方案:网状Meta分析

目的 比较细菌培养药敏试验指导的幽门螺旋杆菌治疗方案和新一线4种方案（伴同疗法、混合治疗、序贯治疗、铋剂四联治疗）的疗效和不良反应，并进行概率排序为临床治疗提供科学依据。方法 系统检索电子数据库，筛选截至2015年6月比较细菌培养药敏试验指导治疗和新一线4种方案，包括基于细菌培养药敏试验指导治疗、伴同疗法、混合治疗、序贯治疗、铋剂四联治疗方案的随机对照试验。通过网状Meta分析和单组率的Meta分析，定量综合这些方案的相对和绝对疗效及不良反应。采用Jadad评分量表评价随机对照试验的方法学质量，构建漏斗图定性测量发表偏倚，其中不对称性检验使用Egger线性回归法或者Begg秩相关法。结果 共纳入20个初治幽门螺旋杆菌感染的随机对照试验，涉及6 753例患者。网状Meta分析表明，细菌培养药敏试验指导治疗的方案显著优于其他方案，根除率最高，不良反应发生率最低；伴同疗法虽然高效但最有可能出现不良反应事件；混合治疗和铋剂四联治疗方案具有较高的疗效、较低的不良反应发生率。结论 对于成年人幽门螺旋杆菌感染，细菌培养药敏试验指导的治疗方案显著优于伴同疗法、混合治疗、铋剂四联治疗和序贯治疗方案；医疗条件匮乏地区可选择混合治疗和铋剂四联治疗方案。     

幽门螺杆菌全菌抗原与尿素酶纯化抗原ELISA检测在人群血清学诊断中的应用

用纯化的Ｈｐ抗原对６７６例各型胃病患者进行了血清抗幽门螺杆菌尿素酶抗体的检测。实验证明其特异性为９６％，敏感性为９８％。血清学ＥＬＩＳＡ检测法，尤其适宜于流行病学调查，还可用于药物治疗效果的观察和筛选非溃疡性消化不良。     

儿童幽门螺杆菌感染血清学研究

应用ＥＬＩＳＡ法对１８１份反复中上腹及脐周痛患儿血清及１９２份对照血清进行了抗幽门螺杆菌ＩｇＧ、ＩｇＭ测定。结果表明：有上述症状患儿血清抗－Ｈｐ ＩｇＧ检出率（５３％）明显高于其他对照组（３４．６％￣３５％），可作为Ｈｐ感染的辅助诊断指标，但其滴度与病程长短及病情严重程度无明显关系，不能反映现症感染。儿童抗－Ｈｐ ＩｇＧ检出率随年龄增加而上升，大年龄组儿童抗－Ｈｐ ＩｇＧ检出率与成人者相近。儿童血     

Prevalence of Helicobacter pylori in asymptomatic subjects—A nested PCR based study

The aim of the study was to see the prevalence of Helicobacter pylori in asymptomatic children and adults by using nested PCR which is considered to be more specific than serological methods. Saliva and stool samples of 137 healthy children (aged 8 months to 16 y) and 108 asymptomatic adults (aged 17–60 y) were collected. PCR with primers targeting Hsp60 gene sequence of H. pylori was used. H. pylori positivity with nested PCR was observed in 45.7% (112/245) of the saliva and 42.8% (105/245) of the stool specimens. Prevalence of H. pylori in saliva was found to be 2.1%, 22.7%, 55.9%, 56.0%, 68.9% and 62.9% in the age groups of <5 y, 6–10 y, 11–16 y, 17–30 y, 31–45 y and 45–60 y, respectively. The detection rates in stool were 4.25% in <5 y, 13.64% in 6–10 y, 50% in 11–16 y, 64% in 17–30 y, 58.62% in 31–45 y and 61.1% in 45–60 y of age groups. The most favourable age group for acquiring the infection was 11–16 y. H. pylori positivity increased with lowering of socioeconomic status. There was no gender bias in prevalence of the bacterium.     

Sterilizing immunity against experimental Helicobacter pylori infection is challenge-strain dependent

The development of a murine model of Helicobacter pylori infection through serial in vivo passage of candidate strains has enabled a quantitative assessment of vaccine efficacy. In this study we compare infection with and protection against challenge from both CagA⁺ type I, and CagA⁻ type II in vivo adapted isolates. In vivo passage of a type II H. pylori isolate resulted in a highly infectious strain (X47-2AL), capable of reproducibly infecting mice to high density (10⁷ CFU/g of gastric tissue). Similarly adapted type I strains were found to colonize mice at a significantly lower level (10⁴–10⁵ CFU/g tissue). Mucosal immunization with recombinant urease (rUre) significantly protected animals against both types. Protection against X47-2AL was characterized by a ≥100-fold (or 2 log) reduction in bacterial density. However, the presence of a residual infection highlighted the inability to achieve sterilizing immunity against this strain. The level of protection appeared independent of challenge dose, and was stable for up to 6 months, all animals exhibiting a low-level residual infection that did not recrudesce with time. Similarly immunized mice challenged with isolates representing the residual infection were also protected, confirming that they did not represent a sub-population of H. pylori that could escape immunity. Immunization and challenge studies with type I adapted-isolates, demonstrated a similar 2–3 log reduction in the bacterial burden, but that in this instance resulted in sterilizing immunity. These results suggest varied specificity for the murine host by different Helicobacter strains that can influence the outcome of both infection and immunity.     

The association of drinking water quality and sewage disposal with Helicobacter pylori incidence in infants: the potential role of water-borne transmission

The mode of transmission of Helicobacter pylori, a bacterium causing gastric cancer and peptic ulcer disease, is unknown although waterborne transmission is a likely pathway. This study investigated the hypothesis that access to treated water and a sanitary sewerage system reduces the H. pylori incidence rate, using data from 472 participants in a cohort study that followed children in Juarez, Mexico, and El Paso, Texas, from April 1998, with caretaker interviews and the urea breath test for detecting H. pylori infection at target intervals of six months from birth through 24 months of age. The unadjusted hazard ratio comparing bottled/vending machine water to a municipal water supply was 0.71 (95% confidence interval (CI): 0.50, 1.01) and comparing a municipal sewer connection to a septic tank or cesspool, 0.85 (95% CI: 0.60, 1.20). After adjustment for maternal education and country, the hazard ratios decreased slightly to 0.70 (95% confidence interval: 0.49, 1.00) and 0.77 (95% confidence interval: 0.50, 1.21), respectively. These results provide moderate support for potential waterborne transmission of H. pylori.     

Helicobacter pylori prevalence in Leipzig’s 1998 school entries: methodology and first results

The non-invasive, stable-isotope-aided Helicobacter pylori (H. pylori) tests- breath and equivalent urine tests- were offered on a voluntary basis as part of the mandatory school entry medical examination to the 1998 school entry cohort of the City of Leipzig (480000 residents). Parents of participating subjects were asked to fill out a detailed epidemiologic questionnaire.The response rate was 94% (n 2228 of 2369 school starters born in 1991/92). Parent-completed questionnaires were returned by 1890 (80%) children. The overall H. pylori positive prevalence was 7.2%. The prevalence among children with a test and a parent-completed questionnaire was 6.5%. Prevalences among subsequently tested family members of the positive tested children was 65,60 and 39% for mothers, fathers and siblings respectively. Though studies have shown that the direct transmission of the bacterium (oral- oral and fecal- oral) is a dominant pathway of infection, the questionnaire analyses indicate associations between H. pylori colonisation and living as well as environmental conditions.     

Therapeutic efficacy of a multi-epitope vaccine against Helicobacter pylori infection in BALB/c mice model

Epitope vaccine is a promising option for therapeutic vaccination against Helicobacter pylori (H. pylori) infection. In this study, we constructed a multi-epitope vaccine with five epitopes and mucosal adjuvant E. coli heat-labile enterotoxin B subunit (LTB) named HUepi-LTB and evaluated its therapeutic effect against H. pylori infection in BALB/c mice model. HUepi-LTB containing three Th epitopes from UreB and two B cell epitopes from UreB and HpaA was constructed and expressed in E. coli. Oral therapeutic immunization with HUepi-LTB significantly decreased H. pylori colonization compared with oral immunization with PBS, and the protection was correlated with antigen-specific CD4⁺ T cells and IgG and mucosal IgA antibody responses. This multi-epitope vaccine may be a promising vaccine candidate that may help to control H. pylori infection.     

Transcutaneous immunization with novel lipid-based adjuvants induces protection against gastric Helicobacter pylori infection

The development of vaccines to combat pathogens that infect across mucosal surfaces has been a major goal of vaccine research. Successful mucosal vaccination requires the co-administration of adjuvants that can overcome the state of immune tolerance normally associated with mucosal application of proteins. In the case of oral immunization, delivery systems are also required to protect vaccine antigens against destruction by gastric pH and digestive enzymes. Furthermore, adjuvants used for mucosal delivery must be free of neurotoxic effects like those induced by the commonly used experimental mucosal adjuvant cholera toxin. Maintenance of the “cold chain” is also essential for the effectiveness of any vaccine and adjuvants/delivery systems that enhance the stability of a vaccine would offer a significant advantage. Needle-free methods of vaccination that induce protective immunity at multiple mucosal surfaces are also desirable for rapid vaccination of large populations. In the present study we show that transcutaneous immunization (TCI) using Lipid C, a novel lipid-based matrix originally developed for oral immunization, containing soluble Helicobacter sonicate significantly reduces the gastric bacterial burden in mice following gastric challenge with live Helicobacter pylori. Protection is associated with the production of splenic gamma interferon and gastric IgA and was achieved without the co-administration of potent and potentially toxic adjuvants, although protection was further enhanced by inclusion of CpG-ODN and cholera toxin in the lipid delivery system.     

遗传变异与幽门螺杆菌感染在胃癌发生中的交互作用

目的  探讨胃癌已知易感遗传变异与幽门螺杆菌(Helicobacter pylori, H. pylori)在胃癌发生中的交互作用,及其对胃癌发生部位和发病年龄的影响。 方法  采用单纯病例研究设计,在2 426例胃癌患者中,通过二元Logistic回归分析模型分析遗传变异与H. pylori之间的交互作用。 结果  调整混杂因素后发现,遗传变异NSUN 3 rs7624041和DEFB rs2376549与H. pylori感染在胃癌发生中交互作用有统计学意义(OR=1.257,95% CI：1.006~1.571,P=0.044;OR=0.845,95% CI：0.715~0.999,P=0.048)。基于肿瘤部位的分层分析发现,遗传变异与H. pylori感染之间不存在交互作用。基于肿瘤TNM(tumor-node-metastasis)分期的分层分析发现,在TNM早期胃癌患者中,遗传变异lnc-POLR3G-4 rs7712641与H. pylori感染交互作用有统计学意义(OR=1.757,95% CI：1.060~2.915,P=0.029)。基于年龄的分层分析发现,在年龄 < 60岁人群中,ASHIL rs80142782、NSUN 3 rs7624041和DEFB rs2376549与H. pylori感染交互作用有统计学意义(OR=1.602,95% CI：1.006~2.551,P=0.047;OR=1.811,95% CI：1.247~2.632,P=0.002;OR=0.688,95% CI：0.520~0.910,P=0.009);而在年龄≥60岁人群中,仅有PSCA rs2294008和CUX 2 rs6490061与H. pylori感染交互作用有统计学意义(OR=0.775,95% CI：0.630~0.954,P=0.016;OR=0.790,95% CI：0.635~0.982,P=0.034)。 结论  胃癌的发生发展较为复杂,通过整合遗传因素和环境因素,针对易感高危人群采取H. pylori的根除措施,将有助于预防胃癌的发生发展。     

Toward the development of a stable,freeze-dried formulation of Helicobacter pylori killed whole cell vaccine adjuvanted with a novel mutant of Escherichia coli heat-labile toxin

No vaccine exists for the prevention of infection with the ubiquitous gastric pathogen Helicobacter pylori, and drug therapy for the infection is complicated by poor patient compliance, the high cost of treatment, and ineffectiveness against drug-resistant strains. A new medical advancement is required to reduce the incidence of peptic ulcer disease and stomach cancer, two conditions caused by infection with H. pylori. Clinical trials have been performed with a formalin-inactivated H. pylori whole cell (HWC) vaccine, given orally in combination with the mucosal adjuvant mLT(R192G), a mutant of Escherichia coli heat-labile toxin. Following the initial dose of this vaccine, some subjects experienced gastrointestinal side effects. To reduce side effects and potentially further increase the amount of adjuvant that can safely be administered with the HWC vaccine, experiments were performed with a form of LT that carried two mutations in the A subunit, a substitution of G for R at position 192, and A for L at position 211. The double mutant LT (dmLT) adjuvant stimulated immune responses as effectively as the single mutant LT in mice. Additionally, following a challenge infection, the dmLT-adjuvanted vaccine was as effective as single mutant LT in reducing gastric urease levels (diagnostic for H. pylori infection), and H. pylori colonization in the stomach as assessed by quantitative analysis of stomach homogenates. A lyophilized formulation of HWC was developed to improve stability and to potentially reduce reliance on cold chain maintenance. It was observed that a dmLT-adjuvanted lyophilized vaccine was equally as protective in the mouse model as the liquid formulation as assessed by gastric urease analysis and analysis of stomach homogenates for viable H. pylori. No readily detectable effect of tonicity or moisture content was observed for the lyophilized vaccine within the formulation limits evaluated. In an accelerated stability study performed at 37 °C the lyophilized vaccine remained equally as protective as vaccine stored at 2–8 °C. The formulation selected for clinical development consisted of 2.5 × 10¹⁰ formalin-inactivated cells per ml in 6.5% trehalose, 0.5% mannitol, and 10 mM citrate buffer at pH 6.8.     

Helicobacter pylori thiolperoxidase as a protective antigen in single- and multi-component vaccines

Helicobacter pylori is an important pathogen of the human stomach, and the development of a protective vaccine has been an enticing goal for many years. The H. pylori antioxidant enzymes superoxide dismutase (SOD) and catalase (KatA) have been shown to be protective as vaccine antigens in mice, demonstrating that the organism's antioxidant enzyme system is a fruitful target for vaccine development. The research described here demonstrates that an additional antioxidant enzyme, thiolperoxidase (Tpx), is effective as a prophylactic vaccine antigen via both systemic and mucosal routes. The functional relationship between SOD, KatA and Tpx also provided an opportunity to investigate synergistic or additive effects when the three antigens were used in combination. Although the antigens still provided equivalent protection when administered in combination, no additional protection was observed. Moreover a decrease in antibody titres to the individual antigens was observed when delivered in combination via the nasal route, though not when injected subcutaneously. The findings of this paper demonstrate that the antioxidant system of H. pylori presents a particularly rich resource for vaccine development.     

Cost-effectiveness of a potential future Helicobacter pylori vaccine in the Netherlands: The impact of varying the discount rate for health

To estimate the cost-effectiveness of a potential Helicobacter pylori (HP) vaccine for the Dutch situation, we developed a Markov model. Several HP prevalence scenarios were assessed. Additionally, we assessed the impact of the discount rate for health on the outcomes, as this influence can be profound for vaccines. When applying the current discount rate of 1.5% for health, the expected cost-effectiveness of HP vaccination is estimated below the informal Dutch threshold of €20,000/LYG when the HP prevalence is assumed ≥20% in the Dutch population. In conclusion, we showed that HP vaccination could possibly be a cost-effective intervention. However, this depends to a large extend on the prevalence of HP in the population. Furthermore, we showed the large impact of the discount rate for health on the cost-effectiveness of a HP vaccination program, illustrative for other vaccination programs.     

Helicobacter pylori infection and gastritis in healthy Nigerians

In a study of forty asymptomatic volunteers from northern Nigeria; 35 (87.5%) had histological gastritis and 32 (80%) were infected byHelicobacter pylori. All but one of the patients infected byHelicobacter Pylori had histological gastritis. This high prevalence ofH. Pylori infection in young, asymptomatic subjects, occurs in an area with a low prevalence of duodenal ulcer. The possible reasons for this are discussed.     

Systemic immunization with an epitope-based vaccine elicits a Th1-biased response and provides protection against Helicobacter pylori in mice

Vaccine-mediated Th1-biased CD4+ T cell responses have been shown to be crucial for protection against Helicobacter pylori (H. pylori). In this study, we investigated whether a vaccine composed of CD4+ T cell epitopes together with Th1 adjuvants could confer protection against H. pylori in a mouse model. We constructed an epitope-based vaccine, designated Epivac, which was composed of predicted immunodominant CD4+ T cell epitopes from H. pylori adhesin A (HpaA), urease B (UreB) and cytotoxin-associated gene A product (CagA). Together with four different Th1 adjuvants, Epivac was administered subcutaneously and the prophylactic potential was examined. Compared to non-immunized mice, immunization with Epivac alone or with a Th1 adjuvant significantly reduced H. pylori colonization, and better protection was observed when an adjuvant was used. Immunized mice exhibited a strong local and systemic Th1-biased immune response, which may contribute to the inhibition of H. pylori colonization. Though a significant specific antibody response was induced by the vaccine, no correlation was found between the intensity of the humoral response and the protective effect. Our results suggest that a vaccine containing CD4+ T cell epitopes is a promising candidate for protection against H. pylori infection.