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Keywords:

  • grandmother;
  • Helicobacter pylori;
  • intra-familial transmission;
  • three-generation households

Abstract

  1. Top of page
  2. Abstract
  3. What is already known this topic
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. References

Aim

Although the prevalence of Helicobacter pylori (H. pylori) increases with age and the main period of acquisition is childhood, the route of transmission of H. pylori infection remains unclear. This study aims to evaluate the relationship between prevalence of children and grandparents.

Methods

A total of 838 consecutive children who attended the Urita clinic and whose blood was taken for work up were enrolled in the present study. They were 449 boys and 389 girls, with a mean age of 12.4 years. H. pylori serology of their family members who were living together in one house was picked up to analyse intra-familial clustering of H. pylori infection. The family members of these children consisted of 448 fathers, 597 mothers, 205 grandfathers, 361 grandmothers and 589 siblings.

Results

The seropositive rates of mothers, grandmother and siblings in seropositive children were significantly higher than those in seronegative children. H. pylori infection in mothers and grandmothers was a marked risk factor for infection in the index children. Larger family size was not a risk factor for H. pylori infection. In contrast, having an infected father or grandfather was not an independent predictor for children infection.

Conclusions

Our data demonstrate that not only mother-to-child transmission but also grandmother-to-child transmission is an important mechanism for the spread of H. pylori in a three-generation household.


What is already known this topic

  1. Top of page
  2. Abstract
  3. What is already known this topic
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. References
  1. Person-to-person transmission within family appears to be the predominant mode of transmission of H. pylori infection.
  2. Mother-to-child transmission is the most relevant source of H. pylori infection.
  3. Infected siblings have a major role in transmission of H. pylori infection to the child.

What this paper adds

  1. Top of page
  2. Abstract
  3. What is already known this topic
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. References
  1. Grandmother-to-child transmission is an important mechanism for the spread of H. pylori in a three-generation household.
  2. Infected grandfathers are not a risk factor for intra-familial transmission of H. pylori infection to the child.
  3. Larger family size is not a risk factor for H. pylori infection in a Japanese rural town.

The prevalence of Helicobacter pylori (H. pylori) antibodies increases with age, and the main period of acquisition is reported to be childhood.[1, 2] However, the route of transmission of H. pylori infection remains unclear. H. pylori infection and its associated pathologies are complex multifactorial entities. The bacterium, host and environment may all play interacting roles in the outcome of infection. Some studies have suggested the possibility of water-borne transmission of H. pylori[1, 3] and the close association with worse living conditions and poorer sanitation.[4] Furthermore, intra-familial clustering of H. pylori infection has been documented,[5, 6] suggesting that exposure opportunity within the family is a strong determinant for the probability of being infected with H. pylori. Because most children are taken care of mainly by their mothers, children of H. pylori-infected mothers are a key source of infection. Actually, Fujimoto et al[7] reported an important role of mother-to-child transmission on being infected with H. pylori in Japanese children aged 6 years and under. In contrast, it has been demonstrated that the prevalence is not different between the children whose fathers are infected and those whose fathers are not infected with H. pylori. It may be because the father has less contact with the child than the mother to the child. Other studies have described that seroprevalence increases directly with family size and that there are close association between H. pylori infection and number of siblings.[8-10]

Clustering of infection within families reinforce the importance of person-to-person spread. Evidence to support both fecal–oral and oral–oral routes has been reported,[11] whereas other findings support the possibility of water-borne transmission.[12, 13] In many Western countries and Japanese big cities, the core household is composed of only two generations (parents and children), whereas the traditional household is still a larger structure combined of three to four generations under the same roof in Japanese rural towns. Because many mothers go to work in the recent years, grandmothers mainly work at home doing the cooking, cleaning and so on. In such a family, it is possible that grandparents may have close contact with children, resulting in the increased opportunity of grandparent-to-child transmission of H. pylori if grandparents are infected. The present study was, therefore, performed to examine prevalence of H. pylori infection in children in a Japanese rural town and the potential for grandparent-to-child transmission.

Methods

  1. Top of page
  2. Abstract
  3. What is already known this topic
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. References

Between April 1999 and December 2004, 838 consecutive children who attended the Urita Clinic and whose blood was taken for work up in clinical practice were enrolled in the present study. They were 449 boys and 389 girls, with a mean age of 12.4 years (range, 1–18 years) (Table 1). The study was carried out in accordance with the Declaration of Helsinki, and informed consent was obtained from all the patients.

Table 1. The age structure of the study population
Age groups (years)Total populationBoysGirls
No.%No.%No.%
1–6789.34051.33848.7
7–911514.06253.05345.3
10–1114717.58155.16644.9
12–1319222.911660.47639.6
14–1515518.57447.78152.3
16–14917.87651.07349.0

Urita Clinic is located in Tsuruta Town with about 14 100 residents. Tsuruta Town is a rural and agricultural village in the Tsugaru district of Aomori prefecture where there are many three-generation households and low-income households. The proportion of elderly people aged more than 70 years is 22%. Waterworks has been established in 1980, and coverage of sewage is 55%. The key industry is agriculture that mainly consists of rice and apple farming.

H. pylori immunoglobulin G antibody concentrations were measured with an enzyme-linked immuno-sorbent assay (ELISA) method (the H. pylori high molecular weight cell-associated proteins). The calculated ELISA is read as positive if the ELISA value is >2.2, negative if <1.8 and indeterminate if it is between 1.8 and 2.2.

Based on the medical records during the same period, H. pylori serology of their family members who were living together in one house was picked up to analyse intra-familial clustering of H. pylori infection. The family members of these children consisted of 448 fathers, 597 mothers, 205 grandfathers, 361 grandmothers and 589 siblings.

Differences in the proportions of H. pylori seropositive children according to the H. pylori serology status of other generations in household were assessed by the χ2 test or Fisher's exact test as appropriate. The association between H. pylori seropositivity of children with that of other generations in their household was assessed using logistic regression analysis adjusting for sex, age group and sibling size. Associations were expressed as odds ratios (ORs) with their 95% confidence intervals (95% CIs).

Results

  1. Top of page
  2. Abstract
  3. What is already known this topic
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. References

The overall seroprevalence of H. pylori was 12.1% (101/838). Thirty children had an indeterminate ELISA value and were excluded from analysis. The study population was categorised into six age groups as shown in Table 1. Subjects in the age group 12–13 years accounted for 22.9% of the overall study population. The prevalence of H. pylori infection increased with age from the 1–6-year age group (7.7%) to the 10–11-year age group (15.6%) and from the 12–13-year age group (7.8%) to the 16-year and over group (18.8%), as shown in Figure 1. The prevalence was highest in the 16-year-and-over group of the study population.

figure

Figure 1. Age distribution of H. pylori infection. image, (−); image, (+/−); image, (+).

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Three hundred and seventy-three family members of seropositive children and 1844 of seronegative ones provided blood for this study. The overall seroprevalence of fathers, mothers, grandfathers, grandmothers and siblings was 58.2% (253/435), 43.4% (251/578), 78.6% (158/201), 68.7% (244/355) and 14.0% (80/571), respectively, when excluding the indeterminate results. Table 2 shows the seropositive rate of family members according to the H. pylori status of children. The availability of the serostatus of mothers, fathers, grandmothers, grandfathers and siblings was investigated separately. Forty-six of the 69 mothers of seropositive children had seropositive results (66.7%), as compared with 205 of 509 mothers of seronegative children (40.3%) (P < 0.01). Similarly, the number of grandmothers of seropositive children with seeropositive results (41 of 47, 87.2%) was significantly higher than the number of seronegative children (203 of 308, 65.9%; P < 0.05). The number of siblings of seropositive children with seeropositive results (61 of 88, 69.3%) was also significantly higher than the number of seronegative children (53 of 459, 11.5%; P < 0.001). Among fathers and grandfathers of seropositive and seronegative children, the numbers with seropositive results were similar, suggesting that having an infected father or grandfather was not an independent predictor for children infection.

Table 2. Seropositive rate of family members according to the H. pylori status of children
Family membersFamily members of seropositive index childrenFamily members of seronegative index children
Serostatus availableSeropositiveSerostatus availableSeropositive
No.%No.%No.%No.%
All tested101   707   
Mothers6968.34666.750972.020540.3
Fathers5049.52958.038554.522458.2
Grandmothers4746.54187.230843.620365.9
Grandfathers1817.81372.218325.914579.2
Siblings8887.16169.345964.95311.5

Results of logistic regression analysis assessing the association between H. pylori seropositivity in parents and likelihood of H. pylori status in 838 children are showed in Table 3. The OR for infection in the index children was 4.8 (95% CI 1.2–19.0) when mothers were infected. Larger family size per se was not a risk factor for infection after adjustment for potential confounders. H. pylori infection in mothers and grandmothers was a marked risk factor for infection in the index children when the infection status of the other family members was taken into account (OR 2.81, 95% CI 1.63–4.99 and OR 3.54, 95% CI 1.47–10.56, respectively). The serostatus of both mothers and grandmothers were studied in 181 children. Fifteen of the 131 children with seronegative mothers and seropositive grandmothers (11.5%) had seropositive results, as compare with two of the 50 children with both seronegative mothers and grandmothers (4.0%). However, the differences did not reach a statistic significance (P = 0.09).

Table 3. Results of logistic regression analysis assessing the association between H. pylori seropositivity in parents and likelihood of H. pylori status in 838 children
  CrudeAdjusted
Odd's ratio95% CIP valueOdd's ratio95% CIP value
  1. CI, confidence interval; N.S., not significant.

MothersSeronegative Ref.  Ref. 
Seropositive3.081.8–5.4<0.00012.811.63–4.99<0.01
FathersSeronegative Ref.  Ref. 
Seropositive1.010.6–1.9N.S.1.020.56–1.93N.S.
GrandmothersSeronegative Ref.  Ref. 
Seropositive3.551.5–10.6<0.013.541.47–10.56<0.05
GrandfathersSeronegative Ref.  Ref. 
Seropositive1.570.4–10.3N.S.1.620.4–10.14N.S.
SiblingsSeronegative Ref.  Ref. 
Seropositive3.392.0–5.8<0.00013.231.86–5.53<0.0001
Family size1–31Ref.  Ref. 
4–50.590.29–1.15N.S.0.580.28–1.14N.S.
6≦1.260.6–2.5N.S.1.190.57–2.38N.S.

In contrast, having an infected father or grandfather was not an independent predictor for index child infection (OR 1.02, 95% CI 0.56–1.93 and OR 1.62, 95% CI 0.40–10.56, respectively). Being part of a sibship with at least one identified infected sibling was positively associated with infection in the index children compared with having only uninfected siblings (OR 3.23, 95% CI 1.86–5.53).

Family size was classified as 2–3, 4–5, or 6 and over family members. There were no significant differences among three groups, suggesting that larger family size was not a risk factor for H. pylori infection in the present study (Fig. 2).

figure

Figure 2. Prevalence of H. pylori infection in children and No. of their family members. image, (+/−); image, (−); image, (+).

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Discussion

  1. Top of page
  2. Abstract
  3. What is already known this topic
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. References

Person-to-person transmission within the family appears to be the predominant mode of transmission. The main source of the infection within the family is not clear yet although the study of family of origin (parental family), as contrasted to family of procreation, originally received attention from epidemiology in the context of childhood infectious diseases. In developed countries, the determining factors for higher prevalence of H. pylori infection have been age, gender, lower socio-economic status, lower education level and large family size.[14-16] Investigations within families found that family members shared the same H. pylori strains, which indicates intra-familial transmission.[17, 18] This study strengthens previous evidence[19] that infected parents, especially infected mothers, play a key role in transmission of H. pylori to the child. In the present study, a significant relationship between seroprevalence of children and their mother, grandmother and siblings was recognised. Although Nguyen et al.[20] also showed intra-familial transmission in a population with several generations living together within the same household, the close association between seroprevalence of children and their grandmother was not found in Vietnam. This suggests that having infected family members, especially mother and grandmother, is highly associated with the infection in children in Tsuruta Town. In most of the families in Tsuruta Town, the mother brings up her children with grandmothers until 6 years of age. Since their mothers return to work in daytime until the child is 1 year of age, grandmothers usually cook their meals. Therefore, children have close contact not only with their mothers but also grandmothers and siblings until they enter the elementary school. Since acquisition of infection occurs in early childhood, it is reasonable that mother, grandmother and siblings might play a key role in transmission of H. pylori to the child as shown in the present study.

In a Japanese report, it has been shown that the infection rate of H. pylori was 8–10% at less than 10 years of age and was about 35% at 30–40 years.[1] Naito et al.[21] reported that the prevalence of H. pylori infection in Tokyo was 4.0–6.7% and was not different among 4-, 7- and 10-year age groups. Since the rate of H. pylori infection in healthy children can vary as a function of age and geographic region, such as between the urban and rural regions of Japan, and since a flow of population into urban cities has been progressed in recent years, a careful evaluation is important in determining the prevalence of H. pylori infection and its route of transmission in Japanese children. Even now, several generations live together within the same household in Japanese rural town like Tsuruta Town. This family structure and their life-style might explain the result that the infection status of grandmother influenced the presence of H. pylori infection in children.

Similar to many previous reports, the present study shows that intra-familial child-to-child and mother-to-child transmission is more important than father-to-child transmissions in three-generation households. Interestingly, our data demonstrate that not only mother-to-child transmission but also grandmother-to-child transmission is an important mechanism for the spread of H. pylori in a three-generation household. Contrary to our expectation, family size is not a risk factor for H. pylori infection, compared among three-generation households.

References

  1. Top of page
  2. Abstract
  3. What is already known this topic
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. References