Faculty Bibliography

The immune response to heat shock protein A (HspA) in Helicobacter pylori-positive adults increases with age in developed countries. This response has not been studied with children or in developing countries (G. I. Perez-Perez, J. M. Thiberge, A. Labigne, and M. J. Blaser, J. Infect. Dis. 174:1046-1050, 1996). As determined by using a specific enzyme-linked immunosorbent assay, HspA seropositivity among 592 individuals in Mexico was <10% in children and increased to >40% in adults

Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations

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

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

DNA rearrangement permits bacteria to regulate gene content and expression. In Helicobacter pylori, cagY, which contains an extraordinary number of direct DNA repeats, encodes a surface-exposed subunit of a (type IV) bacterial secretory system. Examining potential DNA rearrangements involving the cagY repeats indicated that recombination events invariably yield in-frame open reading frames, producing alternatively expressed genes. In individual hosts, H. pylori cell populations include strains that produce CagY proteins that differ in size, due to the predicted in-frame deletions or duplications, and elicit minimal or no host antibody recognition. Using repetitive DNA, H. pylori rearrangements in a host-exposed subunit of a conserved bacterial secretion system may permit a novel form of antigenic evasion

PURPOSE: To examine the relation between serum ascorbic acid and Helicobacter pylori serology from a probability sample of US adults. Subjects and Methods: Data from 6,746 adults (ages 20 to 90 years) enrolled in the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994 were analyzed. Multiple logistic regression models were examined taking into account sample weights and the complex survey design of NHANES III, and controlling for the effects of potential confounders. Because race appeared to modify the association between serum ascorbic acid and seropositivity to H. pylori, we conducted the analyses stratified by race. RESULTS: A total of 2,189 adults (32%) had a positive serology for H. pylori, and, of these, 1,175 (54%) were positive for the CagA antigen. Among whites, a 0.50 mg/dL increase in serum ascorbic acid level was associated with decreased seroprevalence of H. pylori (Odds Ratio (OR) = 0.89, 95% confidence interval (CI) CI 0.82-0.96, p < 0.01). In analyses that controlled for seroprevalence of H. pylori, a 0.50 mg/dL increase in serum ascorbic acid level among whites was independently associated with a decreased seroprevalence of the pathogenic cagA-positive strain of H. pylori (OR = 0.31, 95% CI 0.12-0.79, p < 0.05). Serum ascorbic acid levels were not significantly associated with H. pylori serology among non-whites (all p > 0.05). CONCLUSIONS: Higher serum levels of ascorbic acid were associated with a decreased seroprevalence of H. pylori and of the pathogenic cagA-positive strain of H. pylori among whites. If these associations are related causally and are not the result of residual confounding by factors such as socioeconomic status, ascorbic acid may affect the risk of H. pylori infection and in turn, the risk for peptic ulcer disease and gastric cancer among white Americans

Helicobacter pylori is chiefly acquired in childhood, but the exact timing of acquisition is not well understood. The main goal of this study was to assess H. pylori acquisition in a pediatric population. We studied two cohorts of Native American children: a birth cohort of 50 children and 58 older children (mean age, 53 months). We measured serum immunoglobulin G (IgG), IgM, and IgA antibodies to H. pylori whole-cell antigen and IgG antibodies to CagA. Among 44 birth cohort children monitored for more than 12 months, 24 (54.5%) had seroconversions, 7 (15.9%) were transient, and 17 (38.6%) were persistent. Among the older children, 49 (84.5%) of the 58 children were monitored for 1 year; 34 (69.4%) had H. pylori antibodies at study entry. During the next year, 7 (20.6%) children seroreverted, and of 15 initially negative children, 5 (33.3%) seroconverted. In both groups, evaluation of CagA antibodies increased the sensitivity of H. pylori detection. Serum pepsinogen I (PGI) levels in H. pylori-negative children rose significantly until age 6 months and remained constant for the next 19 months. At the time of H. pylori seroconversion, PGI peaked to levels significantly higher than in the never-seroconverted (P = 0.02) and the pre-seroconverted (P = 0.03) children, but then declined to levels paralleling those of H. pylori-negative children. Thus, H. pylori acquisition, accompanied by a transient PGI increase, was frequent in this population, especially in the second and third years of life, but often was brief

BACKGROUND: Experimental evidences have suggested that a Th1 response is unable to eliminate H. pylori colonization; whereas a Th2 response, like the one induced by vaccination, reduces H. pylori infection in animal models. Some parasitic infections induce a polarized Th2 response, which theoretically would favor a reduced H. pylori prevalence. The aim of this work was to study the possible association between parasitic infections and H. pylori prevalence. MATERIALS AND METHODS: The study population included 120 children and 188 adults from a low socioeconomic level village. H. pylori prevalence was determined in serum by ELISA; parasitic infections were identified in feces by microscopic examination; and total serum IgE levels, as an indirect indicator of some parasitic infections, were determined by ELISA. RESULTS: In children, H. pylori prevalence was no different between those with and without intestinal parasitic infection. By contrast, adults with intestinal parasitic infection had a significantly lower H. pylori prevalence than adults without parasites (62.6% compared with 80.4%; p = 0.006, OR 2.45). Also in adults, but not in children, total IgE levels were significantly higher in those without H. pylori infection than in those with H. pylori infection (p < 0.001). CONCLUSIONS: Intestinal parasitic infections and serum IgE levels showed an age-dependent association with H. pylori prevalence. In adults, but not in children, intestinal parasitic infections and increased IgE levels where associated with a reduced H. pylori prevalence