Determinants of Geographic Variation in Helicobacter pylori Infection among Children on the US-Mexico Border

Kathleen O’Rourke1 , Karen J. Goodman2, Mariah Grazioplene3, Thomas Redlinger4 and R. Sue Day2

1 Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston, SC.
2 University of Texas School of Public Health, Houston, TX.
3 El Paso Satellite Program, University of Texas School of Public Health, El Paso, TX.
4 Department of Biological Sciences, University of Texas at El Paso, El Paso, TX.

Received for publication November 26, 2002; accepted for publication April 2, 2003.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Rates of Helicobacter pylori infection are traditionally higher in developing countries than in developed countries, but the specific reasons for these differences are not fully clear. While chronic diseases resulting from H. pylori are generally of adult onset, chronic infection usually begins in childhood. In this cross-sectional study (1998–2000), the authors compared prevalences of H. pylori infection among children under age 6 years on both sides of the Rio Grande. Participants included 264 children of women from low-income families who were receiving services at health clinics in Juarez, Mexico, or El Paso, Texas, from April 1998 through October 2000. Data were collected through personal interviews and serologic testing for H. pylori antibodies. The crude odds ratio for H. pylori prevalence among Mexican children as compared with US children was 3.94 (95% confidence interval: 1.72, 9.06). After adjustment for covariates, the odds ratio decreased to 1.70 (95% confidence interval: 0.64, 4.52). The adjustments that produced the greatest reduction in the odds ratio for location were those for household crowding and maternal education. This study identified specific factors that may explain geographic variation in H. pylori prevalence among children.

child; Helicobacter pylori ; Mexico; United States

Abbreviations: Abbreviations: CI, confidence interval; IMSS, Instituto Mexicano del Seguro Social; OR, odds ratio; WIC, Women, Infants, and Children.


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Helicobacter pylori infection is responsible for most cases of chronic gastritis, and it is also considered a dominant risk factor for peptic ulcer disease (1) and gastric adenocarcinoma (2). Chronic diseases resulting from H. pylori infection are predominately of adult onset, but initial infection with the organism generally occurs during childhood. Although the major mode or modes of transmission of H. pylori are not fully clear, fecal-oral, oral-oral, waterborne, and zoonotic pathways have been hypothesized.

H. pylori infection is widespread throughout both the developing world and the developed world (3). In developing countries, the majority of people become infected during childhood. In developed countries, on the other hand, a smaller percentage of children are infected, but infection prevalence rises as age increases. In addition, socioeconomic and ethnic differences in H. pylori prevalence have been identified. A serologic study of 2,581 persons aged 6–19 years who were enrolled in the Third National Health and Nutrition Examination Survey (conducted from 1988 to 1994) found weighted seroprevalences of 17 percent (95 percent confidence interval (CI): 13.9, 20.1) for Non-Hispanic Whites, 40 percent (95 percent CI: 34.8, 45.5) for Non-Hispanic Blacks, and 42 percent (95 percent CI: 39.1, 45.0) for Mexican Americans (4). In addition, Mexican Americans born in the United States or Canada had a substantially lower prevalence (37 percent) than those born outside of the United States and Canada (58 percent). In the Third National Health and Nutrition Examination Survey, prevalence was also linked to poverty, household crowding, and low educational attainment by parents.

Reasons for differences in rates of H. pylori infection across countries are difficult to determine because of variation in study designs and population characteristics. Crowding and low socioeconomic status have been found to be associated with H. pylori infection in numerous studies (5, 6). Other studies have identified the following potential risk factors: male gender (7), clustering of H. pylori infection among family members (8, 9), drinking from previously used, unwashed cups (7), poor personal hygiene (7), poor drinking water source (10), lack of indoor plumbing and use of a municipal well (11), raw vegetable consumption (12), and low maternal education (13).

H. pylori infection can be identified through breath testing for active infection or through the use of serologic tests. These tests have excellent accuracy in adults, but validation data relevant to young children are minimal, because of logistic difficulties involved in validating these tests among children. Immunoglobulin G antibodies develop within several weeks of the onset of persistent H. pylori infection (14), and titers decline following elimination of the infection, frequently reverting to seronegativity within 1–2 years, although some persons who eliminate the infection remain seropositive for several years (1519).

The US-Mexico border provides an ideal location for identifying the impact of socioeconomic development on H. pylori prevalence, because of the shared border between a developed country, the United States, and a developing country, Mexico. In this report, we examine factors that contribute to differences in seroprevalence between children on both sides of the Rio Grande.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
We conducted a cross-sectional analysis of the effect of country of residence (United States or Mexico) on the prevalence of H. pylori infection in preschool-age children. The children were older siblings of infants who were enrolled prenatally in the Pasitos Cohort Study, which follows children from El Paso, Texas, and Juarez, Mexico, to investigate determinants of H. pylori infection. At the time of enrollment, from April 1998 through October 2000, a survey was administered to participating mothers, who were recruited during pregnancy, and blood was collected from the women and any of their children who were under age 6 years for H. pylori testing. El Paso participants were recruited at two WIC (Women, Infants, and Children) Program clinics, while Juarez participants were identified at maternal-child clinics of the Mexican Social Security Institute (Instituto Mexicano del Seguro Social (IMSS)) in Juarez. Study personnel were assigned to participating clinics on days when pregnant women were scheduled to visit, and all visibly pregnant women appearing at the clinics were invited to participate in the study. Mothers accompanied by children under the age of 6 years were asked whether a blood sample could be collected from the child; in addition, mothers were encouraged to return with any additional siblings under 6 years of age who had not accompanied them to the initial visit.

H. pylori status was classified using the H. pylori enzyme immunoassay HM-CAP (Enteric Products, Inc., Westbury, New York). The sensitivity and specificity of the HM-CAP enzyme immunoassay were estimated to be 97 percent and 94 percent, respectively, for an adult population (20). Because the HM-CAP assay has not been fully validated in young children, optimal cutoff values are not known. Lower cutoff values may be more appropriate in studies of very young children, who may be slow to develop detectable antibodies in response to H. pylori infection (18, 21). For this study, the adult cutoff values as dictated by the manufacturer were used initially. With use of the adult cutoff values, an enzyme-linked immunosorbent assay value less than 1.8 was regarded as a negative result and a value greater than 2.2 was regarded as a positive result. Values between 1.8 and 2.2 were considered indeterminate. Because of the small number of indeterminate results and evidence from the literature that lower cutoff values may be appropriate for young children, initial model-building was conducted with indeterminate values classified as positive. However, because of the uncertainty of defining an appropriate cutoff value for young children, a sensitivity analysis was conducted. This analysis used three cutoff values: the first with indeterminate values classified as positive, the second with indeterminate values classified as negative, and the last in the middle of the range.

Aside from geographic location of residence (north or south of the Rio Grande), other exposures of interest for this study included demographic factors, socioeconomic indicators, maternal infection status, and hygiene practices. Demographic and socioeconomic factors included child’s age, mother’s education, family income, household crowding, and the presence of a working refrigerator in the home. Data on the following hygienic factors were collected: source of water used for drinking, purification of water, the presence of a latrine or toilet in the home, the presence of an indoor bathroom, and type of excreta disposal system.

The analysis focused on the effect of country of residence on the prevalence of H. pylori infection. A descriptive analysis of H. pylori prevalence by covariate status was performed by location (United States vs. Mexico), using chi-squared tests for categorical data. Logistic regression analysis was used to estimate the odds ratio and 95 percent confidence interval for the effect of geographic location on H. pylori prevalence adjusted for covariates, as well as to estimate the effect of each covariate on H. pylori prevalence.

This study received human subjects protection approval from the Committee for the Protection of Human Subjects of the University of Texas Health Science Center at Houston; the Institutional Review Board of the University of Texas at El Paso; the local and national levels of the IMSS; and the Office for Protection from Research Risks of the US National Institutes of Health.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Of 1,309 pregnant women approached for eligibility screening between April 1998 and October 2000, 1,288 (98 percent) agreed to be screened, 994 were eligible, 807 agreed to participate, and 801 (402 in El Paso and 399 in Juarez; 81 percent of eligible women), all of whom were Hispanic, completed baseline data protocols prior to the child’s birth. Eligibility required an age of 17 years or more, a gestation period of 20 weeks or more, an intention to return to the clinic with the infant after birth, and, after the second year of the study, adequate transportation for returning to the clinic among Juarez participants. The last eligibility criterion was added because transportation difficulties reduced compliance with follow-up in Juarez. In El Paso, on the contrary, participants lived close to the clinics because of WIC residency requirements. Of the 294 ineligible women, 25 were too young, 134 had gestation periods of less than 20 weeks, 110 did not plan to return to the clinic after the child’s birth, and 78 in Juarez did not have adequate transportation for returning to the clinic. (These numbers total more than 294 because some women were ineligible for more than one reason.)

The 801 pregnant women who completed study protocols at baseline had 456 living children under 6 years of age (older siblings of the unborn cohort children). The 456 children came from 385 distinct households (187 in Juarez and 198 in El Paso), of which 322 had one child and 63 had multiple children. Of these children, 264 had blood drawn. Thus, the proportion of eligible children tested for H. pylori status was 69 percent (49 percent in Juarez and 87 percent in El Paso). Although most participants came from one-child households, 11 percent of the participants were multiple children from the same household. A cluster analysis using household as the sampling unit was conducted, but there was no appreciable cluster effect, and therefore a cluster analysis was not used.

The difference between El Paso and Juarez children in participation rates was partly due to a greater reluctance on the part of Juarez mothers to have their child’s blood drawn, as well as more frequent transportation difficulties that precluded returning to the clinic with children not present at enrollment. Because we had data on cohort families with preschool-age children who did not have blood drawn, we were able to compare participants and nonparticipants with regard to key H. pylori risk factors (maternal education, family income, and maternal seroprevalence) (table 1). There were some significant differences between respondents and nonrespondents in El Paso, with respondents being less likely to be from families with higher educational levels and incomes. No significant differences were noted in the Juarez sample.


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TABLE 1. Data on selected sociodemographic factors in families with children tested for Helicobacter pylori and all cohort families with preschool-age children visiting IMSS* clinics in Juarez, Mexico, and WIC* clinics in El Paso, Texas, April 1998–October 2000
 
Table 2 presents H. pylori immunoglobulin G seroprevalences in both Juarez and El Paso, using the adult cutoff values. Of the 92 children tested in Juarez, 13 (14.1 percent) were positive, 71 (77.2 percent) were negative, and eight (8.7 percent) had values that were indeterminate. Of the 172 children tested in El Paso, nine (5.2 percent) were positive, 160 (93.0 percent) were negative, and three (1.7 percent) had indeterminate values. The odds ratio for H. pylori seroprevalence comparing Juarez children with El Paso children was 3.94 (95 percent CI: 1.72, 9.06).


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TABLE 2. Seroprevalence of Helicobacter pylori among children under age 6 years who were accompanying their mothers to prenatal care visits at IMSS* clinics in Juarez, Mexico, and WIC* clinics in El Paso, Texas, by location, April 1998–October 2000{dagger},{ddagger}
 
Table 3 compares the participants’ characteristics at the two study locations. In terms of maternal H. pylori status, seroprevalence was substantially higher among Juarez mothers (72 percent) than among El Paso mothers (49 percent). Juarez children had a higher mean age (3.05 years vs. 2.44 years) and included slightly more males. Overall, Juarez mothers had lower educational levels. Because of the binational characteristics of the study, income levels varied between countries. To facilitate analysis of the effect of relative income level on study location and H. pylori seroprevalence, we ascertained income levels by category (on the basis of US Census categories for El Paso and standard Mexican income categories for Juarez) and grouped incomes into "very low" (El Paso, <$10,000/year; Juarez, <2,000 pesos/month), "low" (El Paso, $10,000–$24,999/year; Juarez, 2,000–5,999 pesos/month), and "moderate" (El Paso, $25,000–$49,999/year; Juarez, >=6,000 pesos/month) levels. More El Paso families than Juarez families had lower income levels, because El Paso families had to be poor enough to qualify for WIC benefits, while there is no upper income limit for qualification for IMSS benefits in Mexico, and most IMSS beneficiaries are employed.


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TABLE 3. Characteristics of children under age 6 years who were accompanying their mothers to prenatal care visits at IMSS* clinics in Juarez, Mexico, and WIC* clinics in El Paso, Texas, by location, April 1998–October 2000
 
Household crowding was much more common in Juarez, with 72 percent of children living in households with more than one person per room as compared with 44 percent of the El Paso children. Minimal differences were noted in sources of drinking water, although children in Juarez were more likely to drink purified water than children in El Paso. Families in Juarez were more likely to have a municipal sewage connection. Among the El Paso families, septic tanks were more common, and few participants did not have some type of sewage disposal. In Juarez, many households had the sewer pipe connected to a bathroom at the edge of the property, and thus the bathroom was not connected to the house. In our study population, 23 percent of households in Juarez had an outdoor bathroom, compared with only 1 percent of El Paso households. Conversely, very few households in Juarez had more than one indoor bathroom (1 percent), while this was more common in El Paso (42 percent). Nearly all participants had working refrigerators, although refrigerator use was closer to universal in El Paso than in Juarez (98 percent vs. 94 percent).

Table 4 presents data on the relation of selected factors to H. pylori infection, stratified by location and for both locations combined. Because of smaller numbers in the stratified analyses, only one variable had a statistically significant association (at the conventional 0.05 significance level) and only in one location (low maternal education in Juarez). There were some differences of moderate magnitude in the impact of variables on infection by site (age, maternal education, and sewage disposal), but because of the small numbers of positive subjects, these findings may reflect random error. When data for both locations were combined, maternal H. pylori seroprevalence, child’s age, low maternal education, and household crowding were associated with prevalent infection in children. In both communities combined, neither drinking water source nor frequency of drinking purified water was clearly associated with infection, while not having an indoor bathroom was related to increased prevalence. The presence of a working refrigerator was associated with infection, although this finding is limited by the fact that few homes did not have a refrigerator.


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TABLE 4. Seroprevalence of Helicobacter pylori among children under age 6 years who were accompanying their mothers to prenatal care visits at IMSS* clinics in Juarez, Mexico, and WIC* clinics in El Paso, Texas, according to selected sociodemographic factors, April 1998–October 2000{dagger}
 
Variables in tables 3 and 4 with a p value of 0.25 or less in both analyses were considered potential confounders in estimation of the effect of geographic location on H. pylori seroprevalence and were included in the multivariable logistic regression analysis. Because of dose-response patterns observed in stratified analysis, the number of indoor bathrooms, household crowding (number of persons per room), and age were modeled as continuous variables. The 16 mothers with an indeterminate H. pylori status were classified as negative. Interaction terms for location and the following variables were examined: age, type of septic system, maternal H. pylori status, number of persons per room, number of indoor bathrooms, and maternal education. Of these, there was evidence of interaction between location and type of septic system (p for interaction term = 0.07), so this term was evaluated in a multivariable model (data not shown). The interaction between septic system and location indicated that in Juarez, children with municipal sewage systems had a higher prevalence of H. pylori than those with septic tanks, while in El Paso, prevalence was greater among children with septic tanks or no waste disposal system. However, because of wide confidence intervals, small numbers in some septic system categories, and collinearity with the main effects for location, as well as limited impact on the other model parameters, the interaction term was not included in the final model.

Table 5 presents prevalence odds ratios for selected study variables using three different cutoff values for the H. pylori antibody test. Although varying the cutoff value resulted in moderate variation in odds ratios and confidence intervals, it had little impact on conclusions regarding the estimated effects. Regardless of the selected cutoff, children living in Mexico had a higher prevalence of infection, and much of the effect of geographic location of residence was eliminated after the data were controlled for other factors. There was a consistent pattern of increased H. pylori prevalence with increased age, increased household crowding, and maternal H. pylori seroprevalence.


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TABLE 5. Adjusted odds ratios for Helicobacter pylori seroprevalence obtained through logistic regression analysis using three different cutoff values for H. pylori among children under age 6 years who were accompanying their mothers to prenatal care visits at IMSS* clinics in Juarez, Mexico, and WIC* clinics in El Paso, Texas, April 1998–October 2000
 
Table 6 presents the effect of each variable in the model on the odds ratio for location. In this table, we first identify the change in the odds ratio for location after inclusion of each variable individually in a base model with only location and that additional variable. We then show the odds ratio for location from models with each variable included sequentially, in descending order by the percentage change noted in the first assessment. Household crowding had the greatest impact on the odds ratio for location, with a 36 percent change, followed by maternal education (20 percent), number of indoor bathrooms (21 percent), and maternal seroprevalence (15 percent). The remaining variables each led to a less than 15 percent change in the odds ratio. When the odds ratio for location was adjusted for both crowding and maternal education, it was reduced considerably, and the lower bound of the confidence interval decreased to less than 1.0. The addition of each subsequent variable weakened the point estimate and resulted in a wider confidence interval.


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TABLE 6. Change in the odds ratio for location with the addition of variables to logistic regression models (location only) for Helicobacter pylori among children under age 6 years who were accompanying their mothers to prenatal care visits at IMSS* clinics in Juarez, Mexico, and WIC* clinics in El Paso, Texas, April 1998–October 2000
 

    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Similar to the findings of other research studies (6, 22), this study found a higher H. pylori seroprevalence among preschool children in a developing-country location (Juarez, Mexico) than in a developed-country location (El Paso, Texas, United States), with a crude odds ratio of 3.94. However, upon adjustment for other factors, the odds ratio decreased to the level of a weak effect in all models. The variables that accounted for most of the crude difference in H. pylori prevalence between the two locations were household crowding and maternal education. The importance of household crowding is consistent with other studies, which have found crowding to be a significant risk factor for childhood infection (4, 7, 10, 23). While other studies have found parental infection status to be associated with the child’s infection status (8, 9, 24), adjusting for it had relatively little impact on the effect of location.

Interestingly, although statistical precision was low, the impact of sewage systems varied between the two countries: children living in homes without a connection to the municipal system had a higher seroprevalence in El Paso, while in Juarez, children with a connection to the municipal system had a higher seroprevalence. This result may have been due to differences between the communities in the quality of sewage disposal systems, although full evaluation of the effect of septic systems was limited by small cell sizes. While more families in Juarez had access to sewage lines, until 1998 the city had no wastewater treatment plant. Thus, the provision of a municipal system in Juarez does not necessarily represent a higher level of sanitation relative to homes in El Paso without municipal connections, most of which have septic tanks. This finding underscores the importance of evaluating specific factors within the context of the community.

Drinking-water quality has also been reported in the literature to be a risk factor for H. pylori infection (11). In the current study, there was no association between drinking-water source or the frequency of drinking purified water and H. pylori infection, although there were differences in these variables between the two locations. Since this was a seroprevalence study, the lack of association may have been due to recent improvements in the water infrastructure of the communities after children had already been infected. Second, information on water purification practices may have been reported less accurately than information on other variables and therefore subject to greater misclassification.

The prevalence of infection among the children in Juarez, Mexico, was much lower than that reported in other studies of children in developing countries. For example, H. pylori prevalences of 23–84 percent have been reported for children aged 5 years or younger in developing countries such as Colombia (10), Peru (11, 25), Chile (26), and Mexico (7). In contrast, the prevalence found in El Paso, Texas, was more comparable to results from other developed countries. For example, prevalences of 5.4–36 percent have been reported for the developed countries of Germany (27), the United Kingdom (28), Greece (29), and the United States (3032). In the Third National Health and Nutrition Examination Survey, Mexican Americans aged 6–9 years had a seroprevalence of 34 percent (4). When the results of this study were compared with the results of the previous study by Redlinger et al. (13), conducted in San Elizario, Texas, a large difference was found. The previous study reported seroprevalences of 36 percent and 24 percent for children aged 4 and 5 years, respectively (13), which was a great increase over the current study result. This difference is probably due to the very young age distribution in this study and the fact that younger children are less likely to show a serologic response.

As in all prevalence studies, a major limitation of this study was the fact that the timing sequence of exposures and onset of infection could not be determined. To establish the timing of these events, one would have to conduct prospective studies. In addition, because of the nature of the location where participants were recruited into the study, information was not obtained directly from the father or other family members. (Factors such as paternal and sibling serologic status and paternal job status may have been important predictors of H. pylori infection in the study participants.) Furthermore, use of antibiotics among the children in this study was not measured. If antibiotic use is frequent in this population, this may partly explain the relatively low seroprevalence found. Reports in the literature have suggested caution when interpreting results of serologic tests for H. pylori in young children, given the uncertainty regarding valid cutoffs for seropositivity; however, our sensitivity analysis suggests that estimates of association based on such results are not highly sensitive to variations in the cutoff value. This lack of sensitivity is probably due in part to the fact that we had relatively few indeterminate values. One additional limitation of our study was the small number of seropositive children, which limited our power to estimate some associations and to fully evaluate interactions.

In summary, our study demonstrates the importance of considering differences in H. pylori risk factors between countries when considering geographic variation in seroprevalence. It underscores the particular importance of household crowding and maternal education in explaining these differences, as well as the need to carefully evaluate the sanitation infrastructure of the study population.


    ACKNOWLEDGMENTS
 
This research was supported by National Institutes of Health grant R01DK53664, cofunded by the Office of Research on Minority Health and the National Institute of Diabetes and Digestive and Kidney Diseases.


    NOTES
 
Correspondence to Dr. Kathleen O’Rourke, Medical University of South Carolina, 135 Cannon Street, Suite 302K, P.O. Box 250835, Charleston, SC 29425 (e-mail: orourkek{at}musc.edu). Back


    REFERENCES
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 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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