Helicobacter pylori infection plays a significant role in the development of chronic gastritis and peptic ulcer disease and is associated with an increased risk of gastric carcinoma. The means of H. pylori transmission and acquisition in early life is poorly characterized.
Infection with H. pylori likely occurs in children younger than 5 years of age.1 A report from Ireland determined the age-specific prevalence of H. pylori infection in children using the C13 urea breath test (UBT). At base-line 28 of 327 (8.6%) index children recruited at the age of 24–48 months were infected and during 4 years of follow-up, 20 additional children became infected.2
The H. pylori stool antigen test (HpSA) is a noninvasive enzyme immunoassay developed for the diagnosis of H. pylori infection and for monitoring response to treatment. The test is a simple, reliable, fast, cheap, and noninvasive method.3,4 We have used the HpSA test to examine the prevalence of H. pylori infection in young children attending day care facilities in Israel.
PATIENTS AND METHODS
Children attending 14 day care facilities (from 3 towns all within a 20-mile perimeter south of Tel Aviv), aged 3–60 months were recruited. One fresh stool sample was collected from the diaper or potty at the day care center from children whose parents consented to testing. The stool was transported in a cooler directly to the laboratory. One hundred fifty-eight of the samples were collected during the summer (July and August), 158 were collected during the following winter (December, January) from children who were not tested during the previous summer. Children started attending day care during September of the year of testing. The samples were either tested on the same day or were stored at −20°C until testing. Specimens were tested using an in vitro qualitative, monoclonal enzyme immunoassay commercial kit (Femtolab, Connex, Germany).
Parents of all children tested, filled out a questionnaire regarding age and gender of the child, family size, residential crowding, parent's education and country of birth of the child and parents. Approvals of the institutional review board of Kaplan Medical Center and the Educational Board of Day Care Centers (Naamat and Wizo) were obtained.
The data were analyzed with SPSS for Windows, version 12, 2005. Comparisons of proportions between the groups were performed by χ2 test analysis. To adjust for potential confounding variables that were significant by univariate analysis, we conducted multivariate logistic regression analysis with HpSA status as the dependent variable.
We tested 316 children, 167 boys (52.8%) (mean age, 18.9 ± 10.9 months) by the HpSA test. Seventy-eight (24.7%) of stool samples were positive and 238 (76.3%) were negative. Ninety-eight (31%) of the children were younger than 12 months, 164 (52%) were between 12 and 24 months, and 54 (17%) were 25–60 months old. Seven (7.1%) of children younger than 12 months tested positive for HpSA as compared with 52 (31%) of the 12- to 24-month-old children and 19 (35%) of the children aged 25–60 months (P < 0.001) (Table 1). One hundred fifty-eight of the stool samples were collected and tested during the summer (July, August) and the rest during the winter (January, February). Sixty-seven (42.4%) of the samples tested during the summer were positive compared with 11 (6.9%) tested during the winter (P < 0.001). The population of children tested during the summer and winter was not the same. The mean age of the children tested during the different seasons was similar. The day care staff did not change throughout the year. Analysis of the data from the parent's questionnaire showed no association between a positive HpSA test and the country of birth of the child or parent, the parents’ education or residential crowding. Almost all the children had been born in Israel, all were Jewish and they were of middle to low socioeconomic background.
The 316 stool samples tested were collected from 14 day care centers. When comparing results among the day care centers to study possible variability among the different centers, we included only those 6 centers in which at least 20 stool samples were tested. Three centers demonstrated high infection rates (>37%) and 3 centers low infection rates (<15%). There was no difference in the socioeconomic factors of the children and their families.
We demonstrated a more than 30% prevalence of Helicobacter infection in infants during the second year of life. Only 7% of the children younger than 12 months were H. pylori positive. There was no difference in the percentage of children positive for HpSA between 12–24 months (31%) and the 25–60 month age group (35%) suggesting that most infections are acquired during the second year of life. This is in concordance with previous studies, which demonstrated acquisition between 2 and 4 years of age.2,4 Our study has the advantage that more than 80% of the children tested were younger than 24 months of age.
The prevalence of H. pylori infection differs in various populations and countries and can be divided into high and low prevalence areas. In developed countries, the acquisition of infection occurs later and at lower rates.1,5
Risk factors for infection include a low socioeconomic background and clustering within families. Day care attendance did not increase the risk of acquisition of infection.1,5 In Israel, studies in adults have shown the overall population prevalence of H. pylori infection to about 70%.6 A recent study by Muhsen et al7 among healthy 3- to 5-year-old Israeli Arab children, reported an H. pylori prevalence of 49.7%. Socioeconomic status, living conditions, and intrafamilial transmission were major risk factors for acquisition of infection in that study. The lower prevalence of infection in our study may reflect the younger age of our group and a more privileged socioeconomic background. Our data further support the observation that the population in Israel has an intermediate-high risk for H. pylori infection and acquisition occurs at an early age.
The major advantages of stool antigen testing are that it is a simple, noninvasive test and that samples can be easily collected. Initial reports about the accuracy of HpSA were encouraging in both adults and children; however, later studies demonstrated a low sensitivity particularly in young children.8,9 The poor performance of HpSA was believed to be caused by inadequate storage and transportation of stool samples or to the polyclonal nature of the test. In a recent study which aimed to validate the UBT and HpSA in children younger than 5 years against invasive histology, the accuracy of noninvasive tests was high; the sensitivity and specificity for the HpSA test, which was determined locally without transportation in 184 children (median age 2.2) was 93.3% and 98.7%.4 An Israeli study comparing invasive (histology and rapid urease testing) with noninvasive testing (HpSA and UBT) in a small group of symptomatic 5-year-old children, found that HpSA was equally effective in diagnosing and confirming eradication of H. pylori with complete concordance between HpSA results and histology.10 In light of these studies and the fact that we used a monoclonal test and performed the stool tests on site, we consider are results reliable for this population based study.
An intriguing finding of this study is that 67 (42.4%) of the samples tested during the summer were positive as opposed to only 11 samples (6.9%) tested during the winter. It is noteworthy that the mean ages of children tested during the different seasons were the same as were the day care staff and facilities. These observations have not been previously reported and must be confirmed or refuted. The fact that H. pylori is more prevalent in the summer may indirectly support the oral-fecal route of transmission, because there are more diarrheal infections during the season and H. pylori might be cotransmitted. Another possible explanation is that during the summer season the children are lightly dressed, making cross infection and exposure to body secretions easier. It must be noted that previous studies have not supported acquisition of H. pylori infection in day care facilities.5
Based on our study we conclude that by 2 years of age up to 30% of infants attending day care facilities in Israel are already infected with H. pylori. The prevalence of the infection during the first year of life is markedly lower suggesting that infection is acquired during the second year of life. The seasonal variation in the number of positive tests warrants further evaluation and consideration.
1. Blanchard TG, Czinn SJ. Helicobacter pylori
acquisition and transmission: where does it all begin? Gastroenterology
2. Rowland M, Daly L, Vaughan M, et al. Age-specific incidence of Helicobacter pylori
3. Husson MN, Rolland C, Gottrand F, et al. Evaluation of a Helicobacter pylori stool antigen
test for the diagnosis and follow-up of infection in children. Eur J Clin Microbiol Infect Dis
4. Dondi E, Rapa A, Boldorini R, et al. High accuracy of noninvasive test to diagnose Helicobacter pylori
infection in very young children. J Pediatr
5. Tindberg Y, Bengtsson C, Granath F, et al. Helicobacter pylori
infection in Swedish school children: lack of evidence of child-to-child transmission outside the family. Gastroenterology
6. Gilboa S, Gabay G, Zamir D, et al. Helicobacter pylori
infection in rural settlements (kibbutzim) in Israel. Int J Epidemiol
7. Muhsen KH, Athamna A, Athamna M, et al. Prevalence and risk factors of Helicobacter pylori
infection among healthy 3-to5-year-old Israeli Arab children. Epidemiol Infect
8. Koletzko S, Feydt-Schmidt A. Infants differ from teenagers: use of noninvasive tests for detection of Helicobacter pylori
infection in children. Eur J Gastroenterol Hepatol
9. Megraud F (on behalf of the European Task Force on Helicobacter pylori
). Comparison of noninvasive tests to detect Helicobacter pylori
infection in children and adolescence: results of a multicenter European study. J Pediatr.
10. Hino B, Eliakim R, Levine A, et al. Comparison of invasive and noninvasive tests diagnosis and monitoring of Helicobacter
infection in children. J Pediatr Gastroenterol Nutr