a Epidemiology Branch, National Institute of Child Health and Human Development, Bethesda, MD, USA.
b US Naval Medical Research Unit-3, Cairo, Egypt.
c Biometry and Mathematical Statistics Branch, National Institute of Child Health and Human Development, Bethesda, MD, USA.
Reprint requests to: Abdollah B Naficy, Epidemiology Branch, National Institute of Child Health and Human Development, Room 7B03, 6100 Executive Boulevard, Rockville, MD 20852, USA.
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Abstract |
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Methods A cohort of children under 36 months, residing in Abu Homos, Egypt, were visited at home twice weekly. Information regarding the child's breastfeeding status was obtained, and periodic anthropometric and household hygiene surveys were performed. In June 1997, a serosurvey was conducted on 187 study participants over 6 months old. The serosurvey was repeated in October 1997. All sera were tested for IgG antibodies to H. pylori.
Results The June prevalence of H. pylori infection was 10%, and the incidence from June to October was 15%. Between June and October, 8 (42%) of 19 children that were positive for H. pylori infection seroreverted to negative. All seroreversions occurred in children 617 months. Other than age, no sociodemographic or environmental factor was significantly associated with incident H. pylori infection. There was no significant differences in the weight-for-age, weight-for-height, and height-for-age z-scores between children with and without prevalent H. pylori infection.
Conclusions Infection with H. pylori is common in Egyptian children under 3 years old and is not associated with malnutrition. No predictors for H. pylori infection were found. Our preliminary evidence for transient H. pylori infections in young children needs to be confirmed in a prospective cohort study, and predictors for persistent infection should be sought, since only these may be relevant to the known sequellae of infection.
Keywords Serology, incidence, prevalence, anthropometry, malnutrition, hygiene
Accepted 13 March 2000
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Introduction |
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There are notable differences in the prevalence of H. pylori infection between developing and developed countries. In many developing countries, H. pylori infection begins in early childhood, with up to 50% of children being infected before the age of 10 years, and 8090% of the population being infected by adulthood. In developed countries, infection rates are significantly lower with less than half of the population infected by adulthood.5,6
It was generally believed that following acquisition of H. pylori, and in the absence of treatment, infection would persist throughout life. However, based on seroepidemiological studies in adults and children from both developing and developed countries, it appears that the spontaneous elimination of H. pylori infection may occur.7
The mode of transmission of H. pylori is not definitively known, however, epidemiological studies suggest person-to-person transmission, by either faecal-oral or oral-oral routes, to be the major mechanism.8,9 In developing countries, there is evidence for both food- and water-borne transmission of H. pylori.10,11 The case for person-to-person transmission is supported by observations that factors such as lower socioeconomic status, lower levels of education, poorer hygiene and sanitation, and household crowding are associated with a higher prevalence of H. pylori infection.6 However, these associations are not inconsistent with food-borne transmission.
To date, there are no published population-based data on the childhood incidence of H. pylori infection in Egypt. This study was aimed to describe the seroepidemiology of H. pylori infection in a population of Egyptian infants and very young children. Our specific objectives were to determine age-specific prevalence and incidence rates of H. pylori infection, to identify sociodemographic and environmental factors associated with incident H. pylori infection, to determine the association between H. pylori infection and the occurrence of malnutrition, and to determine whether there was any evidence for the spontaneous elimination of H. pylori infection in this population.
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Methods |
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Following enrolment, each child was visited at home twice weekly, during which time information regarding the child's diet and breastfeeding status was obtained. In addition, if the child was reported to have loose or watery stools, a faecal specimen was collected. Losses to follow-up recorded at the twice-weekly visits included 13 deaths and 10 out-migrations. At 3-month intervals, the study children were visited in their homes to obtain further information regarding their diet, and to determine their weight and height. Weights were measured to the nearest 0.1 kg using electronic Seca scales. Heights were measured to the nearest 0.1 cm using length boards. In children over 2 years, height sticks were used. Once every 6 months, a hygiene survey was performed for each study participant's household. All home visits and data collection were performed by social workers trained in study procedures.
Anthropometric data obtained in a survey performed on 7 June 1997 were used to evaluate the nutritional status of the children. The indices used to evaluate nutritional status were weight-for-age, weight-for-height, and height-for-age. The indices were standardized by calculating z-scores relative to growth reference curves developed by the National Center for Health Statistics using the Epinut software of Epi Info Version 6.03.12 Stunting and wasting were defined as z-scores of <2 for height-for-age and weight-for-age, respectively. Severe stunting and wasting were defined as z-scores of <3.
Serological surveys
During June and October 1997, blood samples were taken from all participants over 6 months old. In June 1997 blood was obtained from 187 (95%) of the 196 children surveyed. Of the 187 children bled in June, 173 (93%) were bled in October, 1997. Of the 14 children that were bled in June but not October, 12 had left the cohort by virtue of being over 36 months, and two had an insufficient amount of blood drawn. After collection, all blood samples were stored in iceboxes until transported later the same day to the field laboratory in Abu Homos. In the field laboratory, the serum was separated and stored at 20°C until transportation on dry ice to the Naval Medical Research Unit #3 laboratories in Cairo, Egypt, where the serum was tested for IgG antibodies to H. pylori.
Laboratory methods
All sera were tested for IgG antibodies to H. pylori with a commercially available enzyme immunoassay (HM-CAP; Enteric Products, Inc.), and according to instructions given by the manufacturer. ELISA values of <1.8 were considered negative, those >2.2 were considered positive, and those between 1.8 and 2.2 were considered indeterminate. Samples giving indeterminate results were re-tested, and those remaining indeterminate were considered negative. In a sample of US subjects (median age 44 years) the HM-CAP ELISA had a sensitivity of 98.4%, and a specificity of 96.4% for detecting H. pylori infection compared to the 13C-urea breath test.13 In a study that evaluated 169 serum samples from children 018 years old, 3 (1.8%) false positives and 1 (0.6%) false negative occurred when the HM-CAP ELISA was compared with an in-house EIA that had been validated using the 13C-urea breath test or gastric mucosal biopsy.14
Analyses
Prevalence rates of H. pylori infection were calculated by dividing the number of participants positive for H. pylori during the June serosurvey by the total number of participants in the same serosurvey. Incidence rates of H. pylori infection were calculated by dividing the number of participants who converted from negative to positive for H. pylori between the June and October serosurveys by the total number of participants negative for H. pylori during the June serosurvey. Seroreversion rates were calculated by dividing the number of participants who converted from positive to negative for H. pylori between the June and October serosurveys by the total number of participants positive for H. pylori during the June serosurvey.
The independent associations between variables under study and the incidence of H. pylori infection were estimated by multivariate analyses, using logistic regression models. Associations, expressed as odds ratios (OR), were derived from the model coefficients. The variables evaluated as potential predictors of H. pylori incidence were gender, crowding (number of people in household/number of rooms in house), presence of a household latrine, presence of a household garbage container, visible faeces in a household room (sleeping, eating, or cooking room), uncovered garbage in a household room (sleeping, eating, or cooking room), water source for drinking (municipal versus other), whether the house had electricity, maternal education (any versus none), and breastfeeding (any versus none). After adjusting for age, all exploratory variables with statistical significance of 0.05 were included in the multivariate models. In all multivariate analyses, profile likelihood confidence intervals were computed, and statistical significance was defined as a P-value of <0.05 (two-tailed). To evaluate statistically significant differences in the weight-for-age, weight-for-height, and height-for-age z-scores between children who were infected with H. pylori and children who were not, linear regression models were used with adjustments made for potentially confounding variables.
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Results |
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Other than age, no sociodemographic or environmental factor was found to have a statistically significant association with the incidence of H. pylori infection in the study population (Table 3).
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Discussion |
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We found no statistically significant associations between selected sociodemographic or environmental factors and the incidence of H. pylori infection. It is conceivable that we did not find significant associations for variables that have been associated with H. pylori infection in previous studies, such as crowding and lower socioeconomic status,6 because of the limited study sample size.
It has been demonstrated that acute infection with H. pylori can lead to hypochlorhydria, and so we postulated that H. pylori infection may predispose to diarrhoea and malnutrition. Although a study in Gambian children did find a positive association between H. pylori infection and chronic diarrhoea and malnutrition,3,4 no such association was found in another study conducted in Nicaraguan children.17 As in the latter study and another study conducted in Guatemalan children,24 we did not find any significant association between H. pylori infection and malnutrition.
Our results suggest that H. pylori infection is a dynamic process, even in the very young, and raises several important issues that need to be addressed in future studies. Since the currently known sequellae of H. pylori infection are believed to result from chronic infection, it will be important to differentiate between children who have transient H. pylori infections and those with persistent H. pylori infections. How should persistent infection be defined? If, in the absence of definitive therapy only some H. pylori infections persist, are there any socioeconomic, behavioural, or environmental predictors of persistent infection? Similarly, are there any predictors of the ability to clear an H. pylori infection before it becomes persistent? Does persistent infection predispose to other enteric infections, diarrhoea, or malnutrition? Finally, in this population of infants and young children, it will be essential not only to determine the sensitivity and specificity of a commercial ELISA compared with the 13C-urea breath test, but also to determine how each of these diagnostic tests perform with respect to transient or persistent H. pylori infections. We have begun a prospective cohort study of newborns in Abu Homos, Egypt, designed specifically to study the epidemiology of H. pylori infection, which we expect, once completed, to answer these important questions.
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Acknowledgments |
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Financial support was provided by the Naval Medical Research and Development Command (Work Unit No. B6900101. PIX.3270), the National Institute of Child Health and Human Development (Interagency Agreement Y1-HD-718602), the World Health Organization Global Programme for Vaccines and Immunization, and the World Health Organization Control of Diarrheal Diseases Programme.
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References |
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