Helicobacter pylori is one of the most common chronic infections in the world. Colonizing the human stomach, it causes chronic gastritis (1–3), is associated with recurrence of peptic ulcer disease (4–6), and is a risk factor for the development of gastric carcinoma (7,8). The mechanisms by which H. pylori is transmitted is unknown. Seroepidemiologic studies have shown that the prevalence of H. pylori increases with age and is high in developing countries (9–12). It has been suggested that infection is mainly acquired during childhood (13–15). Most of risk factors for H. pylori infection are closely related to poor living conditions in childhood both in developing and developed countries: low socioeconomic level (16–18), poor hygiene conditions and absence of running hot water (19,20), sharing a bed (21), and overcrowding (10,19,22). The prevalence of infection is also high among persons living in closed environments such as orphans (23), submarine crew members (24), and institutionalized patients (25,26), supporting the hypothesis of a person-to-person transmission (27,28).
Most of these epidemiologic studies have been carried out in adults more often than in children. However, pediatric studies directly address the likely main period of acquisition of H. pylori and could thereby more accurately identify epidemiologic risk factors for infection. To identify risk factors associated with H. pylori, we compared living conditions of infected and noninfected children and adolescents and studied the role of the presence of the mother at home and the contact of children with a community (school and nursery) in the epidemiologic characteristics of H. pylori infection.
PATIENTS AND METHODS
During a 2-year period (August 1993–November 1995), all children and adolescents requiring diagnostic or therapeutic upper endoscopy, at the determination of their treating gastroenterologist, were included in the study. Inclusion criteria were the following: age less than 18 years, no history of treated H. pylori infection or past inclusion in this study, no known trouble with hemostasis. Informed consent of parents and of patients, when applicable, was obtained before inclusion in the study.
To avoid an eventual bias related to particular living conditions of neurologically impaired patients (high prevalence of institutionalization), we decided to separate for data analysis patients with neurologic impairment including mental retardation from those free of neurologic impairment. Seventy-seven patients aged 4 months to 16 years (median age, 6 years) were recognized as having a neurologic impairment. Fifty-two of these 77 patients (67.5%) were so impaired that they could neither eat nor move independently. Forty-two of the 77 patients (54.5%) were institutionalized. The other patients lived exclusively in the family home.
We only present here the results of nonneurologically impaired patients.
Esophagogastroduodenoscopy (Upper Endoscopy) and Gastric Biopsies
During upper endoscopy, three gastric antral biopsies (two samples for histologic study and one for bacteriologic study) and two fundic biopsies (one for histologic study and one for bacteriologic study) were taken.
Biopsy specimens were fixed in 10% formalin, embedded in paraffin, and cut at 6 μm. Sections were stained with hematoxylin–eosin–saffron and modified Giemsa technique for light microscopy. All the sections were observed by the same pathologist, who noted the presence or absence of H. pylori.
Biopsy specimens were immediately placed in a transport media (25% cysteinated Ringer) at 4°C and transported within 2 hours to the laboratory. Biopsies were quantitatively plated onto H. pylori specific media: Colombia agar (Pasteur Institut Production, Marnes la Coquette, France) supplemented with 10% horse blood (Eurobio, Paris, France). Plates were incubated at 37°C for 4 to 7 days under microaerobic conditions (10% CO 2 , 5% O 2 ) in a gas regulated incubator (Forma Scientific, Marietta, OH).
Helicobacter pylori Infection
Patients were considered to be infected when H. pylori was present in at least one gastric biopsy specimen, in the histologic analysis, in culture, or a combination thereof. They were considered not infected if both histologic analysis and culture were negative for the five biopsies.
An epidemiologic questionnaire was filled out by the pediatric endoscopist before performing endoscopy. Questions related to the individual's history were as follows: age; gender; patient's and parents' birthplace (developed or developing country); type of housing (house, apartment); number of persons living in housing; number of rooms in housing excluding bathroom and kitchen; father's educational level (I < high school, II ≥ high school); father's occupation according to the INSEE classification (French National Institute for Statistics and Economic Status) and classified as nonworker, manual worker, or nonmanual worker; mother's occupation (at home or worker); and past or present contact with a community (nursery, school, or other). Household density was defined as the number of persons per room (excluding kitchen and bathroom). The cut-off point used in this study to classify homes as overcrowded was one person.
To determine the association between H. pylori infection and epidemiologic factors, data were analyzed using the chi-square test or the Fisher test (depending on the size of the sample; EPI Info software, version 5, CDC, Atlanta, GA). P values less than 0.05 were required for significance. A stepwise logistic regression (SAS Software, Cary, NC) was then performed with variables associated with H. pylori infection in the univariate statistical analysis.
The study was approved by the Research Ethics Committee of the University Hospital of Lille.
Four hundred thirty-six children and adolescents (194 girls, 242 boys), aged 2 days to 17.9 years (median, 2.7 years) were included in the study. On the basis of our diagnostic criteria, 7.3% of the patients (32/436) were infected with H. pylori (28 patients were positive for H. pylori by both histologic analysis and culture, 3 patients were positive only by histologic analysis, and 1 patient was positive only by culture).
Endoscopy was indicated for suspicion of esogastric disorder (71.3%), performing small bowel biopsy (15.8%), suspicion of Crohn's disease, portal hypertension or caustic ingestion (6.9%), follow-up of various gastrointestinal disorders (4.2%), or in a therapeutic aim such as esophageal dilation or perendoscopic gastrostomy (1.8%). The most frequent indication was a suspicion of esophagitis (60.4%) in children fewer than 3 years of age and a suspicion of gastric disorder (38.6%) in children older than 10 years.
Most of the children undergoing endoscopy reported symptoms at the time of inclusion in the study: abdominal pain (n = 193), vomiting (n = 158), digestive hemorrhage (n = 34), other (i.e., anemia, hypotrophy, weight loss, etc.; n = 87). A same child could have more than one symptom at presentation. Thirty-five patients (8%) were asymptomatic at the time of inclusion in the study. However, they all had a medical reason to undergo an endoscopy: suspicion of caustic ingestion (n = 14), follow-up of various gastrointestinal disorders such as coeliac disease or esophagitis (n = 11), follow-up of hepatic disease with portal hypertension (n = 7), and therapeutic aim such as esophageal varices sclerosing (n = 3).
The response rate to each question of the questionnaire varied from 82% to 100%. Results of the univariate analysis are shown in Table 1. Attendance a nursery before the legal age of schooling in France (6 years) was not associated with a higher prevalence of infection. In children fewer than 6 years of age, present contact with a community (nursery, school) also was not a risk factor for H. pylori infection. In children attending nursery at the time of the study or at a younger age, socioeconomic status was the following: the father's educational level was high school or higher in 35 cases (76.1% vs. 61.5% in the entire cohort) and less than high school in 11 cases; the father was a nonmanual worker in 36 cases (78.3% vs. 58.2% in the entire cohort) and a nonworker or manual worker in 10 cases; the mother was working outside the home in 31 cases (64.6% vs. 40.7% in the entire cohort).
Table 2 presents the results of the stepwise regression logistic analysis with H. pylori as the dependent variable. The seven parameters significantly associated with H. pylori in the univariate analysis were entered into the model. Only two factors remained independently associated with H. pylori infection: the age of the patient and the number of persons living with the patient.
Epidemiologic studies have shown evidence for an acquisition of H. pylori primary infection at an early age, both in developing countries (15) and in developed countries (13,14,19). How H. pylori is transmitted and whether transmission mainly occurs at home or in the broader community are not known, but a strong association between H. pylori infection and poor living conditions in childhood clearly has been shown (10,15,19). Childhood therefore appears to be an attractive period to understand better when and how H. pylori is acquired, and studies recently have been realized specifically in children (12,22,29).
The present study was performed in children requiring diagnostic upper endoscopy. This population is not reflective of the population at large, and all results of this study therefore reflect this group of selected patients. However, we tried to minimize this selection bias by inclusion of all children undergoing endoscopy whatever the indication and symptoms.
In this pediatric study, the univariate statistical analysis confirmed the association between H. pylori infection and socioeconomic and demographic factors usually observed in adults and children: infection is more frequent in older patients (10,16,18,30), in children with at least one parent who originated from a developing country (16,31,32) or with a low socioeconomic level reflected in the father's low educational level and occupation as manual worker or nonworker (16,18,20,29) and in children living in overcrowded conditions (19,29,33).
However, in the final model of the study, ethnic origin and socioeconomic level appeared to be confounding factors: with the exception of the age of the patient, only the family size remained independently associated with H. pylori infection. Drumm et al. (27) found that parents of children infected with H. pylori were infected significantly more often than parents of noninfected children, with mothers being infected more than fathers, suggesting the role of familial environment in transmission of H. pylori infection, and especially the eventual role of the relation between the mother and her child. The hypothesis of a major role of mother in transmission of H. pylori is supported by a more recently published study (34) :H. pylori infection in German preschool children is higher if their parents are also infected, with an odds ratio after adjustment for potential confounders two times higher if the mother is infected than if the father is infected. In our study, we were interested in the role of the presence of mothers working at home, supposing that mothers working at home were more frequently in contact with their children than mothers who worked outside the home. This factor has been analyzed very rarely in previous studies. In 684 Colombian children with a high prevalence of H. pylori infection, Goodman et al. (35) observed that children whose mothers were employed outside the home had a lower rate of infection compared with children whose mothers had no earnings. In our study conducted in a developed country, we showed that children whose mothers worked at home were infected no more often than children whose mothers worked outside the home. This result could suggest a possible role of siblings in the transmission of H. pylori infection. In Goodman et al.'s study, after a multivariate logistic regression analysis, the authors indeed found that the strongest predictor of H. pylori status was the number of persons who lived in the home, with the number of children apparently being of greater importance than the number of adults (35). In the same population of children younger than 10 years of age, Goodman and Correa (36) more recently concluded that the odds of infection increased with the number of siblings close in age in the household, and therefore their results support the hypothesis that sibling-to-sibling transmission is a major source of infection.
The hypothesis of person-to-person transmission is also supported by the high prevalence of H. pylori infection reported in communities and closed environments such as an orphanage in Thailand (23), submarine crews (24), institutions for neurologically impaired patients in developed countries (25,37), as well as a day care center (38). In an institution for encephalopathic children located in the north of France, we previously found a very high prevalence of infection (38%) and identified the same strain of H. pylori in 7 of the 45 infected children, 5 of whom lived in the same section of the institution (26). However, even if H. pylori prevalence is high in these communities, factors other than overcrowding are probably important to consider for the acquisition of infection. In the present study, we were interested in other communities, such as nursery centers and schools. We did not find that attendance at nursery centers and school at a young age was at risk of infection in children. Baker et al. (39) did not observe any relation between H. pylori infection and nursery attendance in school children. This could be because of good hygiene conditions in most nurseries and schools in developed countries. In our previous study performed in an institution, encephalopathic children were also living in very good sanitary conditions (26). Moreover, compared with the entire cohort, children attending nursery at the time of the study or at a younger age were from families with a higher socioeconomic status than is supposed to be `protective' against H. pylori infection. This could suggest a predominant role of the family environment in acquisition of infection.
In our group of children, prevalence of H. pylori infection was 7.3%. This rate is under the prevalence rates of 14.1% to 32% usually reported in children in developed countries (16,22,29,40–43). This is probably partly the result of the high number of young children (52% were fewer than 3 years of age) in whom prevalence of H. pylori was the lowest (2.2%). Another explanation for a low prevalence of H. pylori in our group of children is that we excluded from this study neurologically impaired patients in whom a high rate of H. pylori infection is usually reported, from 38% to 76%, especially if they are institutionalized (25,26,37). Indeed, these patients have particular living conditions that may influence H. pylori transmission. In our excluded group of 77 neurologically impaired patients, prevalence of H. pylori infection was 18.2%, higher than in the group of nonneurologically impaired patients (P = 0.02).
Our data show that, in a group of selected young patients, the source of H. pylori infection is intrafamilial rather than in other environments such as nursery and school attended at a young age. Among intrafamilial factors, the number of persons living together is more important than socioeconomic status, and the presence of the mother at home does not appear to influence the rate of H. pylori infection in children. Further studies are necessary to elucidate whether the source of H. pylori could be siblings or the father.
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