Design and participants: Cross-sectional study of 193 eligible African refugee children (aged < 16 years) at their initial health assessment after resettlement in Australia between 1 February and 30 November 2006.
Main outcome measures: (i) Prevalence of H. pylori infection determined by monoclonal faecal antigen enzyme immunoassay testing (MFAT); (ii) associations of H. pylori infection with epidemiological factors (age, sex, transit through refugee camps, comorbidities and treatment interventions).
Results: MFAT was performed in 182 of the 193 children; 149 of these 182 (82%) had H. pylori infection. Age was an independent predictor of H. pylori infection (odds ratio [OR], 1.18; 95% CI, 1.07–1.31). No sex differences were observed. Premigration antimalarial therapy (with sulfadoxine–pyrimethamine and artesunate) significantly reduced the prevalence of H. pylori infection (age-adjusted OR, 0.33; 95% CI, 0.15–0.75).
Helicobacter pylori infection is usually acquired in childhood.1,2 Acute infection is often silent, with symptoms and disease manifesting later in life, as does an increased risk of H. pylori-related malignancy.
The prevalence of H. pylori infection is markedly increased in developing countries,3,4 and risk factors include increasing age, large family size and socioeconomic deprivation.5-7 Refugees resettled in developed countries generally come from regions of high H. pylori prevalence, whereas those who have grown up in industrialised nations have a lower prevalence of H. pylori infection.3,8 Increased prevalence is also found in migrants and indigenous populations; adverse socioeconomic conditions in these groups account for some of the excess risk.7,9,10
Western Australia resettles about 1300 humanitarian refugees annually, representing over 10% of Australia’s refugee intake.11 Currently, many families are African, and about half the refugees are children.12
In this study, we investigated the prevalence and epidemiological associations of H. pylori infection in a high-risk paediatric population. The main outcome measure was H. pylori infection diagnosed by monoclonal faecal antigen enzyme immunoassay testing (MFAT). The effects of age, sex, transit through refugee camps, comorbidities and treatment interventions were investigated.
We conducted a cross-sectional study at the Migrant Health Unit (MHU) in Perth, WA, the sole screening unit for humanitarian refugees resettled in WA. About 80% of targeted refugees in WA receive an initial health assessment at the MHU.12 African children (aged less than 16 years) who presented for initial health assessment between 1 February and 30 November 2006 were included. Blood samples were obtained for routine screening investigations at the first clinic visit as part of standard clinical care and stool samples were collected 1 week later. Children were excluded from our study if they had received antibiotics or proton-pump inhibitors in the preceding month, if they had an immunodeficiency or active tuberculosis. Ethical approval was obtained from the Women and Children’s Ethics Committee, Princess Margaret Hospital for Children. Informed consent was obtained in the presence of trained interpreters, as appropriate.
Data on age, sex, ethnicity, country of last transit, transit period, country of birth, type of dwelling in country of transit, and recent drug administration were obtained at the first visit by means of a structured questionnaire. Breastfeeding history was recorded for children under 2 years of age. Details of premigration antihelminthic and antimalarial treatment were obtained from accompanying International Office of Migration documentation.
Fresh faecal samples were obtained from each child and frozen at − 20°C for batch analyses. We assessed H. pylori status using Amplified IDEIA HpStAR kits (Dako, Glostrup, Denmark) following the manufacturer’s instructions and as previously reported.13
Details of helminth infection, tinea capitis, tuberculosis and malaria were obtained for each child. Helminth infection was defined as the presence of any of the following results: positive serological test for schistosomiasis and/or strongyloidiasis, positive stool microscopy for ova, cysts or parasites of pathogenic helminths, peripheral eosinophilia (≥ 0.7 × 109/L) or elevated immunoglobulin E (IgE) levels (> 280 kU/L). Pre-migration administration of albendazole was documented in 80% of children, with the remainder receiving empiric albendazole at the first health assessment visit.
A clinical diagnosis of tinea capitis was made at the initial visit based on skin examination. Latent or active tuberculosis infection was diagnosed by QuantiFERON-TB Gold testing (Cellestis International, Melbourne, Vic) in children over 2 years of age, with chest radiographs as indicated. All children had a single blood film and smears and rapid immunochromatographic testing (BinaxNOW, Portland, Ore, USA), irrespective of symptoms or premigration antimalarial treatment.
All data were analysed with SPSS, version 14.0 for Windows (SPSS Inc, Chicago, Ill, USA). Continuous variables were compared by independent t tests or Mann–Whitney tests, as appropriate. Associations between categorical variables and H. pylori infection were initially analysed by Pearson χ2 or Fisher’s exact tests. Logistic regression was used to determine the effect of independent variables separately on H. pylori infection, adjusting only for age and sex. Multivariate logistic regression was used to evaluate the effect of covariates on H. pylori infection. Statistical significance was set at the 5% level and two-sided P values were calculated.
Two-hundred and one African refugee children presenting for screening at the MHU were recruited consecutively, with a 100% response rate. Eight children were excluded (five received antibiotics before screening and three were of non-African ethnicity). Of the 193 eligible children, 100 (52%) were male. The mean age was 7.9 years (SD, 4.4 years). Box 1 shows the main demographic features of the cohort.
Eighteen children (9%) were breastfeeding at the time of enrolment (mean age of breastfeeding children, 11.3 months; SD, 5.2 months). There were 116 children (60%) who had lived in refugee camps, with the remainder living in urban dwellings (apartments or houses). Almost all children who transited through Tanzania or Kenya (96 of 97; 99%) had lived in refugee camps, while all 28 who transited through Egypt had lived in apartments. The overall median transit time before resettlement in WA was 5.5 years (interquartile range [IQR], 3.0–8.4). Protracted refugee stays (more than 5 years in transit) were common (98 of 193; 51%); the median transit time for these 98 children was 8.0 years (IQR, 6.5–10.0).
MFAT was performed in 182 children, and H. pylori infection was diagnosed in 149 (82%). MFAT results clearly discriminated between populations that were infected (median positive optical density [OD], 2.85; IQR, 1.18–3.61) and uninfected (median negative OD, 0.10; IQR, 0.08–0.18), with no equivocal results (P < 0.001).
Children with H. pylori infection were significantly older (mean age, 8.5 years [SD, 4.2] v mean age, 5.8 years [SD, 4.5]; P < 0.001) with no sex differences. The prevalence of H. pylori infection was 63% for children under 2 years of age, rising to 95% for those older than 14 years. When analysed by age strata, the odds of infection were more than fourfold higher for children aged over 10 years compared with those aged less than 5 years (odds ratio [OR], 4.42; 95% CI, 1.58–12.35). Where two or more children in a family were enrolled (51 families), 45 of the 51 oldest siblings (88%) had H. pylori infection compared with 35 of the youngest siblings (69%; OR 3.43; 95% CI, 1.21–9.67).
Logistic regression was used to assess the effect of various factors on the odds of H. pylori infection (Box 2). Age was a significant predictor of H. pylori infection, with the odds of infection increasing by 17% for each year of age (OR, 1.17; 95% CI, 1.07–1.28). While the odds of infection were numerically largest for children transiting through Kenya, the overall relationship between country of transit and infection was not significant after adjusting for age and sex. Premigration antimalarial treatment (79 of 182 children; 43%) significantly reduced the odds of H. pylori infection after adjusting for age and sex (OR, 0.31; 95% CI, 0.14–0.72). Multivariate regression showed that only age and premigration antimalarial treatment were significantly associated with H. pylori infection (Box 3).
In total, 76 of the 182 children (42%) had evidence of helminth infection, 15 (8%) had tinea capitis, 16 (9%) had Plasmodium falciparum infection, and 11 of the 153 children (7%) tested had positive QuantiFERON-TB Gold results (with normal chest radiographs), indicative of latent tuberculosis infection. After adjusting for age and sex, the prevalence of H. pylori infection was not affected by the presence any of these infections (Box 2). No difference in IgE levels or peripheral eosinophilia counts were found in children with or without H. pylori infection (data not shown).
Our study shows a high prevalence of H. pylori infection in African refugee children, confirming that children from developing countries are at greater risk of infection.14 Our results support the observation that early childhood is the main period of acquisition of H. pylori infection in high-prevalence populations.1,2,4 H. pylori infection was present in 82% of this cohort, and the odds of infection increased significantly with age. In comparison, the prevalence of H. pylori infection in Australian children is low,8 although the prevalence in Australian Aboriginal children is significantly higher, especially in those from remote areas,9 reflecting differences in socioeconomic status.
The protective effect of antimalarial treatment on H. pylori infection is a potentially important and unexpected finding. In children who received empirical premigration antimalarial treatment, this was given about 6 weeks before study enrolment. This correlated with the median time between arrival in Australia and the MHU health screening (Dr A Thambiran, Medical Director, MHU, Perth, WA, personal communication). Empirical premigration antimalarial treatment was ceased in mid 2006 because of concerns about efficacy and coverage.15
The antimalarial therapy may have eradicated existing H. pylori infection. The period between administration of antimalarial drugs and collection of faecal samples was short, and so reacquisition of H. pylori infection during this intervening period is unlikely. The elimination half-lives of pyrimethamine and sulfadoxine are relatively long (3–4 and 6–9 days, respectively) and that of dihydroartemisinin, the active metabolite of artesunate, is less than 1 hour.16 Antimalarial therapy is unlikely to have affected MFAT performance. The effect of antimalarial therapy remained significant in our final regression analyses, and was independent of albendazole therapy. To our knowledge, this in-vivo association has not been previously reported, although artemisinins are known to have antibacterial properties.17 It has been postulated that artemisinin derivatives may interact with iron-dependent bacteria (such as H. pylori) and potentially provide a mechanism for targeted bacterial death.18 The possible therapeutic role of artemisinins, which are cheap and well tolerated, in H. pylori eradication warrants further investigation.
A limitation of our study is the lack of a traditional “gold standard” for the diagnosis of H. pylori infection. Methods based on endoscopy and biopsy, or urea breath testing, are neither practical nor ethical for population-based screening of children, particularly in non-English speaking and often traumatised families. Recent international guidelines now recommend MFAT as an alternative in both adult and paediatric populations.19,20
In this study, we investigated potential epidemiological risk factors that may predispose refugee children to H. pylori infection. Surprisingly, transit through refugee camps did not place children at increased risk of infection, despite harsh environmental and nutritional conditions. The ubiquitous deprivation and overcrowding that characterise urban refugee conditions (eg, Egyptian apartments) may instead contribute to the non-significant association between dwelling type and H. pylori infection.
Intrafamilial spread of H. pylori, particularly mother-to-child transmission2,21,22 or from infected older siblings,2,23 is a potentially important mechanism for acquisition. In our cohort, older siblings had odds of H. pylori infection three times higher than those of their youngest siblings, supporting this premise. Parental H. pylori infection was not assessed in this study, but a high prevalence would be expected, in keeping with analogous published results.22-24 Reliable data on family size could not be obtained, as many siblings and/or parents were displaced in transit.
The relationship between breastfeeding and infection was not found to be statistically significant; however, the number of children being breastfed at the time of enrolment was small. Our study did not address the phenomenon of transient H. pylori infections.25 Over 60% of children aged under 2 years had H. pylori infection, which is similar to other reports of African infants.4 Given the high levels of overall infection in this cohort, reinfection is likely even if there were cases of transient infection in infancy.
Clinicians should be aware of the high prevalence of H. pylori infection in resettled refugee children, including the potential development of chronic complications. Longitudinal studies of this population are warranted.
1 Ethnicity, country of birth and transit profiles of the 193 African refugee children in the study
2 Adjusted odds ratios for factors tested for independent associations with Helicobacter pylori infection
3 Multivariate logistic regression model of variables associated with Helicobacter pylori infection
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