Faculty Bibliography

ABSTRACT This review summarizes key results of epidemiologic studies published in peer-reviewed journals between April 2003 and March 2004. The prevalence of H. pylori infection continues to vary strongly between developing countries and developed countries, and according to ethnicity, place of birth and socioeconomic factors among people living in the same country. Intrafamilial spread appears to play a central role in transmission of the infection in both developing and developed countries. The role of H. pylori infection in development of noncardia gastric cancer appears to be even much stronger than previously assumed, whereas the lack of an association with cardia cancer and an inverse association with adenocarcinoma of the esophagus could be confirmed. Suggestions for an inverse association of the infection with atopic diseases have recently received further support, whereas evidence concerning the role of the infection (or its eradication) in GERD and a large variety of other extragastric diseases, including cardiovascular disease, remains inconclusive

Helicobacter pylori is the primary cause of peptic ulcer disease and an etiologic agent in the development of gastric cancer. H. pylori infection is curable with regimens of multiple antimicrobial agents, and antimicrobial resistance is a leading cause of treatment failure. The Helicobacter pylori Antimicrobial Resistance Monitoring Program (HARP) is a prospective, multicenter U.S. network that tracks national incidence rates of H. pylori antimicrobial resistance. Of 347 clinical H. pylori isolates collected from December 1998 through 2002, 101 (29.1%) were resistant to one antimicrobial agent, and 17 (5%) were resistant to two or more antimicrobial agents. Eighty-seven (25.1%) isolates were resistant to metronidazole, 45 (12.9%) to clarithromycin, and 3 (0.9%) to amoxicillin. On multivariate analysis, black race was the only significant risk factor (p < 0.01, hazard ratio 2.04) for infection with a resistant H. pylori strain. Formulating pretreatment screening strategies or providing alternative therapeutic regimens for high-risk populations may be important for future clinical practice

The vacA and cagA genotypes of 50 Helicobacter pylori isolates from patients in the north-eastern region of Mexico were characterised by PCR, and the correlation between genotypes and different clinical outcomes was investigated. Strains of H. pylori that are vacA s1/m1 and cagA positive have previously been associated with more severe clinical outcomes, and some studies have shown differences in the vacA and cagA genotypes in different geographical regions. The six possible combinations of the vacA signal (s) and middle (m) regions were identified in this population, and the most frequent genotype was s2/m2. Thirty-two (64%) isolates were identified as cagA-positive. The s region was not amplified from seven of the cagA-positive isolates, and the m region was not amplified from one cagA-negative isolate, indicating that additional subfamilies of s and m genotypes may exist. The s1/m1 genotype was associated with cagA-positive strains (p < 0.05). No association was found between the vacA and cagA genotypes and clinical outcomes

BACKGROUND: The goal of this study was to determine the importance of Helicobacter pylori CagA+, VacA+, and HLA-DQA1 alleles in a Mexican population with gastric cancer (GC). METHODS: We studied a group of Mexican patients (cases) with distal GC (n=22) or high-grade dysplasia (HGD; n=8) (mean age, 62.7 years, F : M=0.3; age range, 33-84 years) and 77 ethnically matched non-GC controls (mean age, 47.1 years; F : M=1.96; age range, 17-92 years). Both cases and controls were H. pylori-positive by at least two of the following diagnostic tests: rapid urease test, histology, culture, or serology. The presence of antibodies to CagA and VacA proteins was determined by Western blot, and the HLA-DQA1 typing was carried out by a polymerase chain reaction (PCR) sequence-specific primer method. RESULTS: The carriage of H. pylori CagA+, VacA+ strains was associated with GC or HGD (odds ratio [OR], 6.07; 95% confidence interval [CI], 1.56-27.57; P=0.005). The allele frequency of DQA1*0503 was significantly lower in the GC-HGD group than in the non-GC group (OR, 0.13; 95% CI, 0.02-0.59). Logistic regression analysis identified the carriage of HLA-DQA1*0503 as an independent protective factor for GC (OR, 0.19; 95% CI, 0.04-0.94) and colonization with H. pylori CagA+, VacA+ strains as an independent risk factor for GC (OR, 6.15; 95% CI, 1.69-22.37). CONCLUSIONS: Infection with H. pylori CagA+, VacA+ strains represents a significant risk for the development of GC. The absence of HLA-DQA1*0503 could be a host risk factor for the development of GC in Mexican patients

Serum samples were obtained from 215 farm-resident children and 396 non-farm-resident children living in a defined rural Wisconsin population. Antibodies to Campylobacter jejuni and Escherichia coli O157:H7 lipopolysaccharide (O157 LPS) immunoglobulin G were measured, and the incidence of clinic visits for diarrheal illness was determined. Risk factors were assessed in a telephone interview. There were 363 children (59%) with C. jejuni antibodies (seropositive for >/=2 immunoglobulin classes) and 86 (14%) with O157 LPS antibodies. Increasing age and farm residence were independently associated with C. jejuni seropositivity by multivariate analysis. O157 LPS antibodies were independently associated with increasing age, female sex, manure contact, and sheep contact. The incidence of clinically recognized diarrhea was similar among children with and without antibodies to C. jejuni and O157 LPS, but the clinic visit rate for diarrhea was 46% lower among farm-resident children. These results are consistent with reduced occurrence of clinical illness from repeated antigenic stimulation in a farm environment

Prevalence of Helicobacter pylori varies among different geographic regions. The aim of this study was to assess H. pylori prevalence in symptomatic patients in northeastern Mexico and its possible association of H. pylori with disease.We studied 261 symptomatic patients (female/male 1.44, mean age 53 years) who underwent gastrointestinal endoscopy at Hospital Universitario Dr. Jose Eleuterio Gonzalez in Monterrey, Nuevo Leon, Mexico. Among patients included in this study, 209 (80.1%) had nonulcer dyspepsia (NUD), 30 (11.5%) peptic ulcer disease (PUD), and 22 (8.4%) high-grade dysplasia or gastric cancer. H. pylori status was determined by histology, positive rapid urease test, culture, or IgG whole-cell anti-H. pylori. Specific IgG antibodies for CagA status were determined by ELISA as previously described. Patients were defined as infected with H. pylori by positive results of two or more diagnostic tests used.Overall prevalence of H. pylori was 67.8%. According to clinical presentation, gender (male) was related with gastric cancer (p <0.01) and with PUD (p <0.05). Of 177 patients infected with H. pylori, 90 (50.8%) were seropositive for CagA antigen; in addition, H. pylori CagA+ was more common in patients with PUD (77.8%) than with NUD (43.2%) (p <0.05). However, no association was found between gastric cancer patients and presence of CagA+ H. pylori strains.H. pylori prevalence in symptomatic patients in northeastern Mexico is as high as the prevalence reported for the entire country. We confirmed that patients with gastric cancer and PUD are more likely to be male. CagA+ strains were associated with patients who presented PUD but not gastric cancer

Available commercial tests for the diagnosis of Helicobacter pylori infection are based on different types of antigen preparations and hence the diagnostic utility differs substantially. OBJECTIVE: To assess the diagnostic value of the determination of Immunoglobulin (Ig) A and IgG antibodies to H pylori whole cell (WC) and IgG antibodies to cytotoxin associated gene A (CagA) using an in-house ELISA in relation to the results obtained with different invasive methods. METHODS: The study population consisted of 251 Mexican adults, mean age 53 years, age range 15 to 92 years and female to male ratio of 1.5. Peptic ulcer disease was present in 10.8% of these patients, 5.2% had gastric cancer, 11.2% had esophagitis and 72.9% had nonulcer dyspepsia. Biopsy specimens from the body and the antrum of the stomach were obtained for culture, histology and rapid urease test. ELISAs to detect IgA and IgG WC and CagA antibodies were performed using serum. RESULTS: H pylori status was established by the results of the invasive tests. Eighty (31.9%) patients positive to the three tests and 38 (15.1%) negative to all the tests were identified. Based on this result, the sensitivity and specificity of the serology assays were 97.5% and 78.9% for the IgG WC and 70% and 73.7% for the IgA WC, respectively. However, if H pylori status was defined by the positive result of at least one or two invasive diagnostic tests, the sensitivity for the IgG WC decreased to 87.3% and 66.7% respectively, but the specificity was essentially the same. Similar results were obtained for the sensitivity and specificity of IgA using the same criteria. A low CagA prevalence was observed (39%). CONCLUSIONS: Testing for serological IgG antibodies to H pylori WC was the best to assess whether infection by H pylori was present. Neither the IgA WC nor the IgG CagA ELISAs add significant value in the diagnosis of H pylori

Helicobacter pylori, a chronic gastric pathogen of human beings, can be divided into seven populations and subpopulations with distinct geographical distributions. These modern populations derive their gene pools from ancestral populations that arose in Africa, Central Asia, and East Asia. Subsequent spread can be attributed to human migratory fluxes such as the prehistoric colonization of Polynesia and the Americas, the neolithic introduction of farming to Europe, the Bantu expansion within Africa, and the slave trade