Hoda M. Malaty

Effect of Treatment of Helicobacter pylori Infection on the Long-term Recurrence of Gastric or Duodenal Ulcer: A Randomized, Controlled Study

OBJECTIVE To determine the effect of treating Helicobacter pylori infection on the recurrence of gastric and duodenal ulcer disease. DESIGN Follow-up of up to 2 years in patients with healed ulcers who had participated in randomized, controlled trials. SETTING A Veterans Affairs hospital. PARTICIPANTS A total of 109 patients infected with H. pylori who had a recently healed duodenal (83 patients) or gastric ulcer (26 patients) as confirmed by endoscopy. INTERVENTION Patients received ranitidine, 300 mg, or ranitidine plus triple therapy. Triple therapy consisted of tetracycline, 2 g; metronidazole, 750 mg; and bismuth subsalicylate, 5 or 8 tablets (151 mg bismuth per tablet) and was administered for the first 2 weeks of treatment; ranitidine therapy was continued until the ulcer had healed or 16 weeks had elapsed. After ulcer healing, no maintenance antiulcer therapy was given. MEASUREMENTS Endoscopy to assess ulcer recurrence was done at 3-month intervals or when a patient developed symptoms, for a maximum of 2 years. RESULTS The probability of recurrence for patients who received triple therapy plus ranitidine was significantly lower than that for patients who received ranitidine alone: for patients with duodenal ulcer, 12% (95% CI, 1% to 24%) compared with 95% (CI, 84% to 100%); for patients with gastric ulcer, 13% (CI, 4% to 31%) compared with 74% (44% to 100%). Fifty percent of patients who received ranitidine alone for healing of duodenal or gastric ulcer had a relapse within 12 weeks of healing. Ulcer recurrence in the triple therapy group was related to the failure to eradicate H. pylori and to the use of nonsteroidal anti-inflammatory drugs. CONCLUSIONS Eradication of H. pylori infection markedly changes the natural history of peptic ulcer in patients with duodenal or gastric ulcer. Most peptic ulcers associated with H. pylori infection are curable.

Epidemiology of Helicobacter pylori in an asymptomatic population in the United States: Effect of age, race, and socioeconomic status

A causative role is now accepted for Helicobacter (formerly Campylobacter) pylori in type B gastritis, and evidence is accumulating that H. pylori infection plays a major contributory role in peptic ulcer disease. Preliminary studies have reported that the prevalence of H. pylori infection increases with age, but detailed information on the prevalence of the bacteria in any defined population and on the factors that may influence the pattern of distribution remains scanty. In the present study, a sensitive enzyme-linked immunosorbent assay and a [13C] urea breath test were used to investigate the prevalence of H. pylori infection among 485 healthy asymptomatic volunteers between the ages of 15 and 80 residing in the Houston metropolitan area. H. pylori infection was present in 52%. The prevalence of H. pylori infection increased rapidly with age at 1%/yr for the overall population. The frequency of H. pylori infection was higher in blacks (70%) than whites (34%) (P less than 0.001); this difference remained after adjustments were made for age, gender, educational level, income, and use of tobacco or alcohol. H. pylori infection was independent of gender but was closely correlated with socioeconomic class. There were significant inverse correlations between age-adjusted frequency of H. pylori infection and income and between educational level and H. pylori infection. There was no association between H. pylori infection and consumption of alcohol or nonsteroidal antiinflammatory drug use or smoking. Having pets was associated with a lower frequency of H. pylori infection, but this was highly associated with higher socioeconomic status. The mode(s) of transmission of H. pylori is unknown, but the social patterns of H. pylori infection are consistent with fecal-oral transmission as one important pathway. Socioeconomic factors seem to determine the age of acquisition.

Seroepidemiology ofHelicobacter pylori infection in India

Helicobacter pylori (previouslyCampylobacter pylori) is now accepted as the major cause of type B gastritis and thus what is known about the epidemiology of type B gastritis can reasonably be transferred toH. pylori. We used a specific ELISA for anti-H. pylori IgG to study the prevalence ofH. pylori infection in a population of lower socioeconomic class from Hyderabad, India. The results from India were compared to studies from other parts of the world. Two hundred thirty-eight individuals ages 3 to 70 participated. The frequency ofH. pylori infection increased with age (P<0.01) and was >80% by age 20.H. pylori infection was present in 79% of the population studied; there was no gender-related difference in prevalence ofH. pylori infection. IgG antibody against hepatitis A (HAV) was rapidly acquired in Hyderabad; in a subset of 58 children between the ages of 3 and 21 tested, the frequency of anti-HAV was 98.2%. The prevalenc ofH. pylori infection increases with age in both developed and developing countries. The high age-specific prevalence ofH. pylori infection in developing countries is probably a reflection of the lower socioeconomic level of those areas.

Age at acquisition of Helicobacter pylori infection: a follow-up study from infancy to adulthood

BACKGROUND Helicobacter pylori infection is common worldwide, but the time of acquisition is unclear. We investigated this issue in a cohort of children selected retrospectively from a population followed up for 21 years. METHODS We monitored 224 children (99 black, 125 white; 110 male, 114 female) from 1975-76 (ages 1-3 years) to 1995-96. H pylori status was assessed by presence of serum IgG antibodies. FINDINGS 18 (8.0%) children at age 1-3 years had H pylori antibodies (13% black vs 4% white children, p=0.008). By age 18-23 years, the prevalence of the infection was 24.5% (43% black vs 8% white participants, p< 0.0001). Of the 206 children not infected at baseline, 40 (19%) became infected by age 21-23. The crude incidence rate per year was 1.4% for the whole cohort, ranging from 2.1% at 4-5 years and 1.5% at age 7-9 years to 0.3% at 21-23 years. The seroconversion rate was higher among black than among white children (relative risk 3.3, 95% CI 1.8-6.2, p=0.001). The median age for seroconversion was 7.5 years for both races. Nine of the 58 seropositive children cleared the infection during follow-up. The rate of seroreversion per year was 1.1%; it was highest among children at age 4-5 years (2.2% vs 0.2% at ages 18-19). INTERPRETATION Most newly acquired H pylori infections happened before age 10 years. Treatment and preventive strategies should be aimed at children in this age-group.

Helicobacter pylori Infection: Genetic and Environmental Influences: A Study of Twins

An association exists among Helicobacter pylori infection, histologic gastritis, and peptic ulcer disease [1-7]. Considerable data have been published about the epidemiology of H. pylori infection; however, the sources and the modes of transmission of H. pylori infection remain unclear. The reservoir for H. pylori infection is probably humans. The primary route of transmission is unknown, but any method that introduces the organism into the stomach of a susceptible person may lead to infection. Clustering of H. pylori organisms among family members has been reported [8-11]. Whether this reflects the importance of a genetically influenced general susceptibility factor, a common-source environmental factor, or person-to-person transmission remains unclear. In 1875, Galton [12] pointed out the value of twins for studying the relative importance of heredity and environment. Subsequently, twin studies have proved to be a valuable method for investigating the genetic component of traits. The basic tenet is that if a trait (for example, H. pylori infection) has no genetic component, the trait is displayed equally by both members of monozygotic twin pairs and by both members of dizygotic twin pairs. Greater similarities within monozygotic twin pairs suggest the involvement of genetic effects. One of the most powerful study designs to examine the relative importance of genetic and environmental variation for individual differences in susceptibility to infection is to compare the results of identical twins separated at an early age with those of twins who were reared together. By comparing twins reared together with twins reared apart, it is possible to estimate the importance of rearing environment on twin similarity. We investigated the relative importance of genetic and environmental factors on the acquisition of H. pylori infection by studying twins separated at an early age and reared apart and twins reared together [13]. Methods Sample We studied twins from a subregistry of the Swedish Twin Registry, which includes entries for about 25 000 twin pairs born in Sweden between 1886 and 1958. The subregistry consists of a number of twins who indicated that they were separated before the age of 11 years (and were reared apart) and of a sample of twins who were reared together; all these twins were matched on the basis of sex, date, and county of birth [13]. This sample is used in the Swedish Adoption-Twin Study of Aging. When this aging study was initiated in 1984 with a mail-out questionnaire, both twins were alive from 591 twin pairs reared apart and from 627 twin pairs reared together. Two years later, a subset of twin pairs reared together and reared apart in which both members responded to the first questionnaire was invited to participate in an examination that included health evaluation and administration of cognitive tests. Both members of 291 pairs who were 50 years of age or older and 12 pairs younger than 50 years participated in this in-person testing phase. This represents 60% of all pairs 50 years or older in which both responded to the first questionnaire. If one twin in a pair declined participation in the in-person testing phase, the co-twin was not invited to participate (resulting in a lower pairwise participation rate). A follow-up of twins declining participation indicated that cognitive decline and poor health were the major reasons for unwillingness to participate. The average age at the time of testing was 65.6 years (SD, 8.4); 60% of the twins were women. The present analyses include 36 pairs of monozygotic twins reared apart, 64 pairs of monozygotic twins reared together, 88 dizygotic pairs reared apart, and 81 dizygotic pairs reared together for whom serum samples were available. Zygosity diagnoses were first made using physical similarities and were confirmed using the serologic assay. One pair was excluded from the analyses because adequate certainty of zygosity (>98%) could not be obtained. The distribution of age at separation is highly skewed: 52% of the twins reared apart were separated before their first birthday, 69% by their second birthday, 82% by the age of 5 years, and all by the age of 11 years. Reasons for separation varied; most were separated because of the death of one or both parents or economic hardship (or both). Further details of the procedures, sample, and design of the Swedish Adoption-Twin Study of Aging are described by Pedersen and colleagues [14]. Helicobacter pylori Assay The presence of anti-H. pylori IgG was assessed using the commercially available high-molecular-weight cell-associated protein H. pylori immunoassay (Enteric Products Inc, Westbury, New York). The test was scored positive when the optical density was 32.0. The test has a sensitivity greater than 98% and a specificity greater than 95% [15]. Helicobacter pylori infection is chronic and even lifelong. After successful antimicrobial agent therapy, the antibody titer is not detectable within a year; thus, the presence of serum antibody is a reliable indication of H. pylori status. Statistical Analysis As a preliminary indication of the importance of genetic effects for H. pylori infection, probandwise and pairwise concordances were calculated for monozygotic and dizygotic twins, reared apart and reared together. A greater concordance for monozygotic pairs than for dizygotic pairs suggests the importance of genetic effects. Pairwise concordances were calculated as the percentage of pairs concordant for expressing H. pylori among the total number of pairs in which at least one member was infected with H. pylori. Probandwise concordances represent the number of affected twins in concordant pairs divided by the number of proband patients infected with H. pylori. The latter form of concordance is more genetically meaningful because it can be compared with risk figures for other family groups. The primary aim of the analyses was to describe individual differences in the acquisition of H. pylori infection by partitioning these differences (total variance) into genetic and environmental variance components. Quantitative genetic theory posits that total phenotypic variance is the sum of genetic variance plus environmental variance and is twice the covariation of genetic and environmental effects. Genetic variance can be further partitioned into additive genetic variance, reflecting the effect of many segregating genes of equal effect, and into nonadditive genetic variance because of interactions within and among genetic loci. Environmental variance can be partitioned into environmental effects shared by family members (causing familial similarity) and into nonshared environmental effects (causing differences among family members). An assumption of the present analyses, that no genotype-environment covariance exists, has been supported for most behavioral and biomedical phenotypes [16]. Heritability is defined as the proportion of total variance attributable to genetic variance. In these models, all variance that is not genetic is considered environmental. Thus, the heritability statistic provides an estimate of the relative importance of genetic differences for individual differences in susceptibility to H. pylori infection in the sample of twins (relative to environmental effects). This statistic refers to the sample and does not describe risk to an individual. Intraclass Correlations Several methods exist to estimate heritability [16]. Nonadditive genetic effects are indicated when monozygotic correlations are more than twice the magnitude of dizygotic correlations. The intraclass correlation of monozygotic twins reared apart provides a direct and unbiased estimate of heritability. The influence of shared rearing environment can be estimated by comparing correlations of twins reared apart with those of twins reared together. The effect of correlated environments in an adoption-twin study refers to all similarities that cannot be explained by genetic factors or shared rearing environments. The effect of correlated environment may reflect prenatal influences and similarities in adult life experience (such as degree of contact when the twins are adults) and is estimated by subtracting the estimate of heritability from the intraclass correlation for monozygotic twins. Residual variance that is not explained by heredity, shared rearing environment, or correlated environments is attributed to nonshared environmental effects unique to the individual. Model-Fitting Analysis The variance comparisons of correlations and their interpretations are summarized in Table 1. Examination of intraclass correlation provides valuable insights about the relative importance of genetic and environmental factors. However, it is difficult to estimate the importance of several variables (for example, heritability, nonshared environment, shared rearing environment, and other forms of correlated environment) by separate comparisons of pairs of correlations. Model-fitting analyses are more powerful because the data from all four groups identified by zygosity status and rearing status (rearing-by-zygosity groups) are weighted appropriately and because tests of alternative models are permitted. The models for fitting are based on quantitative genetic expectations of factors contributing to twin similarities and differences. Table 1. Comparison of Correlations and Their Interpretations The model used in the present study (Table 1) has been described in detail by Neale and Cardon [17]. Because the phenotype (presence of H. pylori infection) is categorical (0 or 1), tetrachoric intraclass correlations were calculated using the PRELIS program (Scientific Software, Inc., Chicago, Illinois) for each of the four rearing-by-zygosity groups. Expected correlations based on the model for the four rearing-by-zygosity groups were fitted to the observed tetrachoric correlation matrices using a maximum likelihood estimation procedure in Lisrel VII (Scien

Rising incidence of inflammatory bowel disease among children: a 12-year study.

Objective: Data suggest an increase in the incidence of pediatric inflammatory bowel disease (IBD). We examined the trend of the incidence of IBD in children. Patients and Methods: A retrospective investigation was conducted on a cohort of children diagnosed with IBD between 1991 and 2002 who were registered in the IBD center at Texas Childrens Hospital. The diagnosis of IBD was based on clinical, radiological, endoscopic, and histological examinations. Results: There were 272 children eligible for the analysis; 56% diagnosed with Crohn disease (CD), 22% with ulcerative colitis (UC), and 22% with indeterminate colitis. The male-to-female ratio was 1.2:1 in CD, 0.6:1 in UC, and 0.8:1 in indeterminate colitis. From 1991 to 2002, the incidence rate has doubled from 1.1/100,000/year (95% confidence interval [CI] 0.85–1.36) to 2.4/1001,000/year (95% CI 2.10–2.77). This trend was valid for CD but not for UC. Whites had higher incidence rate of IBD than African Americans or Hispanics: 4.15/100,000/year (95% CI 3.48–4.82) versus 1.83/100,000/year (95% CI 1.14–2.51), and 0.61/100,000/year (95% CI 0.33–0.89), respectively. African Americans were predominantly diagnosed with CD. Conclusions: The results demonstrate the rising incidence of IBD among children with evidence of more CD than UC. Recognition of these results will have important implications for diagnosis and management of IBD in children.

Transmission of Helicobacter pylori Infection Studies in Families of Healthy Individuals

Helicobacter pylori is accepted as the commonest cause of type-B gastritis. Detailed information about the mode of transmission remains scanty. We investigated the frequency of H. pylori infection within families, defined as consisting of a husband and wife with at least one biologic child, all living in the same household. Inclusion criteria required that both the parents and the children had been born in the United States, had used no antibiotic or bismuth for the previous 2 months, had no recent major illness or surgical operation, and had no symptoms referable to the upper gastrointestinal tract. H. pylori infection was identified with a 13C-urea breath test and an enzyme-linked immunosorbent assay for anti-H. pylori IgG. Forty-one families (151 healthy individuals) were enrolled. Before the results of the H. pylori tests were known, one parent was selected as the index subject. H. pylori infection clustered; that is, 68% of spouses of H. pylori-infected index subjects were also H. pylori-infected, compared with 9% of spouses of H. pylori-negative index subjects (p less than 0.0001). The children of infected index parents were also more likely to be infected than children of uninfected index parents--40% versus 3%, respectively (p less than 0.0001)--and the results in the children were independent of whether the father or the mother was the index subject. Clustering of H. pylori infection within families suggests person-to-person transmission or common source exposure. The high frequency of H. pylori infection in spouses suggests that genetic factors are less important than living conditions for transmission of H. pylori infection.

Acquisition versus Loss of Helicobacter pylori Infection in Japan: Results from an 8-Year Birth Cohort Study

Studies of the pattern of change in the epidemiology of Helicobacter pylori infection are scarce. A longitudinal cohort study consisted of 644 children and adults, and two independent cross-sectional surveys were conducted in rural Japan between 1986 and 1994. The anti-H. pylori IgG seroconversion rates were 1.1% and 1% per year for children and adults, respectively. The seroreversion rate per year was 1.8% for children and 1.5% for adults. The cohort study was confirmed by the two cross-sectional studies. H. pylori prevalence fell in all age groups in both children (odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.2-1.0, P = .05) and adults (OR = 0.4, 95% CI = 0.3-0.6, P = .001). The rate of loss of H. pylori infection was greater than the acquisition. Data regarding acquisition and loss of H. pylori infection are critical to understanding the epidemiology of the infection and to developing treatment and vaccination strategies.

Natural History of Helicobacter pylori Infection in Childhood: 12-Year Follow-up Cohort Study in a Biracial Community

We assessed the pattern of acquisition and loss of Helicobacter pylori infection in a cohort of 212 children from a biracial community with a homogeneous socioeconomic class. The children were followed over 12 years (1973-1974 to 1985-1986) from childhood to young adulthood. H. pylori status was assessed by the presence of serum IgG antibodies to H. pylori. At ages 7-9, 19% of children had H. pylori infection (40% of blacks vs. 11% of whites; P = .0001); 12 years later, 33% were seropositive. The higher prevalence among blacks remained (P = .0001). During follow-up, 22% of children became infected; the rate of acquisition was fourfold greater among blacks than among whites (P = .001). Over the 12-year period, infection was lost in 50% of whites compared with 4% of blacks who either remained infected or became reinfected. H. pylori infection in childhood is affected by both acquisition and loss of infection in different ethnic groups. This observation is critical for understanding the epidemiology and transmission of H. pylori infection.

Helicobacter pylori Infection in Preschool and School-Aged Minority Children: Effect of Socioeconomic Indicators and Breast-Feeding Practices

Helicobacter pylori infection was examined among 356 asymptomatic white Hispanic and black children aged 2--16 years attending 13 licensed day care centers in Houston. Demographic information and socioeconomic factors were evaluated. H. pylori status was determined by (13)C-urea breath testing. The prevalence of active H. pylori infection was 24% and increased with age. Prevalence was almost identical among white Hispanic and black children. Children living in the most crowded conditions were at the greatest risk for H. pylori acquisition, and an inverse correlation was seen between the mothers education and H. pylori positivity in children. Breast-feeding played a protective role against the acquisition of H. pylori infection. Understanding the epidemiology of H. pylori infection in childhood requires better understanding of the interactions between environment, ethnic group, and socioeconomic conditions.