Helicobacter pylori seropositivity in children with chronic ... : Saudi Journal of Gastroenterology (original) (raw)
Since the discovery of Helicobacter pylori (H. pylori) by Warren and Marshall[1] two decades ago, evidence has been accumulating to indicate that it plays a significant role in the development of chronic gastritis, peptic ulcer diseases, mucosa-associated lymphoid tissue lymphoma, and gastric cancer.[2] Factors such as age, socio-economic level and living conditions, especially during childhood, have been postulated as important determinants in the acquisition of the microorganism. [3] Seroepidemiologic investigations have indicated that infection with H. pylori is very common throughout the world[4] and most infections are acquired during childhood. [5] The prevalence of H. pylori infection in children in developing countries is higher, and begins at a younger age, than in developed countries.[6]
It is well known that H. pylori colonization of the gastric mucosa stimulates the release of various proinflammatory substances, such as cytokines, eicosanoids and proteins of the acute phase.[7] Moreover, a cross mimicry between bacteria and antigens exists in H. pylori infected patients. [8] Therefore, a pathogenetic link between H. pylori infection and diseases characterized by activation of inflammatory mediators and/or induction of autoimmunity might exist.[9] The association between H. pylori infection and some of the chronic diseases such as diabetes, allergy, anemia, neurological impairment, and Down's syndrome in children had previously been reported.[101112]
Seroanthropological investigations have been useful adjuncts in improving our understanding of the co-evolution of humans and infecting microorganisms. Microbiological and histological methods, as well as polymerase chain reaction and urea breath test, have been used to assess H. pylori infection; however, it has been stressed that, in children, the specific immunoglobulin G (IgG) test may provide a useful tool in the diagnostic work-up of H. pylori infection.[13]
The aim of the current study was to determine the prevalence of H. pylori infection in Jeddah, Saudi Arabia, with a well-established ELIZA technique among asymptomatic children as well as in chronically diseased children (diabetes, chronic asthma, chronic anemia, neurological impairment and Down's syndrome). The seroprevalence of H. pylori was evaluated according to nationality, age, sex and severity of the disease.
Patients and Methods
Serum samples were collected over a 2-year period between October 2001 and October 2003 from a total of 1432 children attending outpatient clinics at King Abdulaziz University and Maternity & Children's Hospitals, Jeddah Saudi Arabia.
The participants comprised 543 asymptomatic children who served as controls, and 889 children suffering form chronic disease [diabetes (n=61); chronic asthma (n=220); chronic hemolytic anemia (n=347); neurological impairment (n=237); Down's syndrome (n=24)]. Study participation was voluntary, and written informed consent was obtained from parents and from the older children. The Medical Ethics Committee of King Abdulaziz University approved the study. Non of the participating patients complained of any specific symptoms that might be attributable to infection with H. pylori, such as gastrointestinal bleeding and abdominal pain.
Children taking antimicrobial drugs during the 2 months prior to the study, those taking immunosuppressive or chemotherapeutic drugs, and those with primary or secondary immunodeficiency diseases were excluded from the study.
Serum samples were stored at -20C until use. The sera were tested for H. pylori IgG with a commercially available enzyme linked immunosorbent assay kit (HM-CAP; Enteric Products Incorporation, Westbury, NY). Using control sera, specimens were tested in duplicate according to the manufacturer's specifications,[14] which categorize results as negative, indeterminate, or positive if absorbance values (for sera diluted 1:100 at 450 nm) are <1.8, 1.8 to 2.2, or <2.2 units, respectively. Consistent results (both positive and negative) were classified accordingly; discordant or indeterminate results were repeated and if they remained indeterminate, the patients were excluded from additional analyses. The sensitivity and specificity of the kits were 98% and 94%, respectively.[15]
Statistical analysis
Data were recorded and analyzed by the author using Epi Info (version, 6.04; CDC).[16] Odds ratio was used to determine the strength of association between the study outcome (H. pylori infection) and any factor believed to influence its risk. Further, the 95% confidence bounds were determined to test whether the strength of association is statistically significant. Mantel-Haenszel Chi-squared tests were used for statistical analysis. and values of P <0.05 were accepted as significant. Seroprevalence rates were compared by nationality, sex, age and severity of illness.
Results
543 asymptomatic children were enrolled in the study, 286 Saudi (52.7%) and 257 non-Saudi (47.3%) of which 335 were boys (61.7%) and 208 were girls (38.3 %). Of the 543 asympatomatic children studied, positive titers for H. pylori were found in 128 children (23.6%). There was no significant difference in the prevalence of infection between non-Saudi and Saudi children (12.7% versus 10.9%, p<0.09) or in boys compared to girls (14.9% versus 8.7%, p<0.67) [Table 1].
Prevalence of Helicobacter pylori among asympatomatic children with nationality and gender variable.
However, the prevalence of H. pylori infection significantly increased with age, ranging from 12.9% in the 1-5 year age, to 22.2% in the 6-9 year age and to 33.8% in the 10 year age groups, (p<0.001). This increase in prevalence with age was found among all the asympatomatic subgroups, in Saudi (p<0.01), non-Saudi (p<0.01), males (p<0.001) and females (p<0.05) [Table 2].
The frequency of risk of Helicobacter pylori infection in relation to age, nationality, gender within asympatomatic children.
Patients with type I diabetes did not differ significantly in the prevalence of H. pylori infection compared with control (34.4% versus 23.6%, p<0.06), with odds ratio 1.71 and confidence limits (CI: 0.94-3.11) [Table 3]. There was no-significant difference in the H. pylori prevalence related to nationality, gender and increase age (p<0.76, p<0.93, p<0.68, respectively) [Table 4][Table 5] but significant difference related to the duration of illness (p<0.01) [Table 6].
In chronic asthmatic patients, the prevalence of H. pylori infection did not significantly differ from control (20.4% versus 23.6%, p<0.36), with odds ratio (0.84) and confidence limits (CI: 0.56-1.25) [Table 3]. There were no significant differences related to nationality and gender (p<0.42, p<0.96, respectively) among patients [Table 4]. However, there were significant differences in H. pylori seroprevalence related to age (p<0.01). The increase in prevalence with age was more apparent among Saudi and male patients (p<0.05, p<0.05 respectively) but not among non-Saudi and female patients (p<0.17, p<0.12 respectively) [Table 5]. No significant differences related to the duration of illness, number of hospital admission and number of ER visits (p<0.13, p<0.55, p<0.44, respectively) were reported [Table 6].
Chronic hemolytic anemia patients showed increase in the prevalence of H. pylori infection versus controls (31.7% versus 23.6%, p<0.01), with odds ratio (1.15) and confidence limits (CI: 1.11-2.07) [Table 3]. There were no significant difference related to nationality and gender (p<0.40, p<0.79, respectively) [Table 4]. However, significant differences in H. pylori seroprevalence related to increasing age (p<0.01) were reported. The increase in the prevalence with increase age was significantly among Saudi and male patients (p<0.05, p<0.05 respectively) but not among non-Saudi and females patients (p<0.06, p<0.25 respectively) [Table 5]. There were significant associations between H. pylori seroprevalence with duration of illness and number of blood transfusions (p<0.001, p<0.05, respectively) [Table 6].
In patients suffering from neurological impairment, the prevalence of H. pylori infection significantly differed from controls (32.1% versus 23.6%, p<0.05), with odds ratio (1.54) and confidence limits (CI: 1.08-2.18) [Table 3]. There were no significant differences related to nationality and gender (p<0.91, p<0.80, respectively) [Table 4] but a significant difference related to increasing age (p<0.01). The increase in prevalence with age was more apparent among male patients (p<0.05) but not among non-Saudi, Saudi and females patients (p<0.07, p<0.09, p<0.69 respectively) [Table 5]. There were significant differences in H. pylori seroprevalence related to the duration of illness, number of hospital admissions and mode of feeding (p<0.001, p<0.05, p<0.01, respectively), but not with mobilization (p<0.56) [Table 6] were reported. In patients with Down's syndrome, the prevalence of H. pylori infection did not significantly differ from controls (29.2% versus 23.6%, p<0.52), with odds ratio (1.34) and confidence limits (CI: 0.49-3.53) [Table 3]. There were no significant difference related to nationality and gender (p<0.19, p<0.21, respectively) [Table 4].
The difference of risk of Helicobacter pylori infection in chronically diseased children compared with control.
Association of Helicobacter Pylori seropositivity with nationality and gender variable within various groups of chronically diseased children.
The frequency of risk of Helicobacter pylori infection in relation to age, nationality, gender within chronically diseased children.
The frequency of risk of Helicobacter pylori infection in relation to different categories within chronically diseased children.
Discussion
Although H. pylori organisms have been isolated worldwide, they are more frequently recovered from patients in developing countries.[6] This cross-sectional population-based serosurvey demonstrates that the prevalence of H. pylori infection among asympatomatic children in Jeddah, Saudi Arabia was 23.6%. It was not related to nationality or gender. In consistency with others[171819] a significant increase in the seroprevalence of H. pylori infection among asympatomatic children by age was found. It has been reported that the difference in seroprevalence of H. pylori for each age group increased by approximately 1% per year.[20] A previous study in Riyadh, Saudi Arabia reported rapid increase in the prevalence of H. pylori infection with age from 40% at 5-10 years old to 70% at 20 years old[17].
Metabolic derangements that occur in diabetes may impair a number of host defenses in both humoral and cellular immunity.[21] It has been speculated that alterations in the glucose metabolism may promote H. pylori colonization,[22] which could be due to reduced gastric motility[23] or by chemical changes in gastric mucosa due to non-enzymatic glycosylation of mucins or increased sialic acid[24] which may be involved as a receptor for H. pylori on the cell surface[25] by promoting adhesion of H. pylori to gastric mucosa cells.
The current study revealed increased risk of H. pylori infection among type I diabetic children compared to controls, but the difference did not reach the significant level. The increased risk was not related to nationality, gender and age; on the other hand it was associated significantly with increase in the duration of illness. In this context, some investigators did not find any association between H. pylori infection and diabetes mellitus,[26] meanwhile others showed a lower seroprevalence of H. pylori in type I diabetic patients compares with controls.[2728] Some authors have suggested an increasing prevalence of H. pylori among diabetic patients.[29] However, the validity of those findings has been severely criticized.[30] The great heterogeneity of results reported in the different studies could be due to methodological differences. Many studies have not reported the method used for selecting cases and control subjects, or used a small sample size. It had been reported that, children with type I diabetes and H. pylori infection had an increased daily insulin requirement compared with the requirement of their uninfected peers and eradication of H. pylori infection was associated with better control of glycemia.[31] In consistence with some authors[329] and in contrast with others,[33] the result of this study did not reveal increased risk of H. pylori infection in chronic asthmatic patients compared to asymptomatic children. A significant association between seroprevalence of H. pylori and increasing age was reported. On the other hand, it was not related to nationality, gender, duration of illness, number of hospital admission and number of ER visits.
Novel epidemiological data from a cross-sectional survey showed that in active H. pylori infection patients, the prevalence of asthma, eczema, and allergic rhinitis is lower than in H. pylori-negative subjects.(12)
H. pylori infection is usually associated with chronic diseases; one of them is chronic anemia. In consistence with others,[343511] the results of the present study showed a significant increase in the prevalence of H. pylori infection in chronic anemic patients compared to asymptomatic children.
This study reported significant association between prevalence of H. pylori in studied chronic hemolytic anemic children with increase age, duration of illness and number of blood transfusions, meanwhile no association with nationality and gender was reported. Association between H. pylori infection and recurrent abdominal pain in school-age children with sickle cell anemia[3637] and iron deficiency anemia[10] had been reported.
Those participants who suffered from neurological impairment as reported in other studies,[3839] showed a significant increased in the prevalence of H. pylori seropositivity compared to asymptomatic children. The prevalence of infection was significantly related to increase in age, duration of illness, number of hospital admissions and mode of feeding, suggesting that H. pylori seropositivity frequently develops at our institution. An increased prevalence of H. pylori seropositivity in institutionalized patients with neurological impairment had been suggested by other authors.[394041] The factors responsible for a higher prevalence of H. pylori seropositivity in institutionalized patients with neurological impairment have not been elucidated but may include domestic crowding and other conditions, such as length of stay and age of the residents.[40] In agreement with other reports,[39] this study shows that H. pylori seropositivity in institutionalized patients with neurological impairment is not associated with specific symptoms.
Mentally disabled children may be at higher risk of infections because of different feeding abilities, toileting needs, and living and sanitary arrangements. No significant difference was reported in this study between risks of H. pylori infection within children suffering from Down's syndrome compared to asymptomatic children. The prevalence also was not related to nationality and gender. On the other hand, It had been reported by Bohmer et al.[38] that intellectually disabled persons and employees with close physical contact to them for a considerable period are at high risk of developing H. pylori infection.
In conclusion, the serosurvey described here found a high prevalence of H. pylori-specific IgG among asympatomatic and with chronically diseased children in Jeddah, Saudi Arabia.
The prevalence of H. pylori seropositivity in children suffering from chronic disease (chronic anemia, neurological impairment) have higher risk of infection than asymptomatic children. The rate of seropositivity went up with increasing age in asympatomatic children and those suffering from chronic asthma, chronic anemia and neurological impairment children. Also, there was an association between the prevalence of H. pylori seropositivity and duration of illness, number of hospital admissions, number of blood transfusions and mode of feeding in the chronically diseased children studied.
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Keywords:
H. pylori; seroprevalence; diabetes; chronic asthma; chronic anemia; neurological impairment
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