Exploring childhood immunization among undocumented migrants in Sweden - following qualitative study and the World Health Organizations Guide to Tailoring Immunization Programmes (TIP).

OBJECTIVES: National vaccination coverage in Sweden is high. Recurrent outbreaks of measles and rubella however highlight some immunity gaps in the population. Current knowledge about immunization status of undocumented migrant children is scant. The World Health Organization/Europe has developed the Guide to Tailoring Immunization Programmes (TIP) to assist countries in diagnosing barriers and motivators to vaccination in communities with low vaccination coverage. Based on the TIP guide, the objective of this study was to explore determinants to vaccination among undocumented immigrants, using qualitative approach. STUDY DESIGN: The study consisted of three steps: (i) an initial workshop for problem statement; (ii) qualitative research for increased understanding of the vaccination practices of children in the undocumented community; and (iii) a second workshop to incorporate the qualitative interview findings together with data from key stakeholders into a conceptual framework. METHODS: This was a qualitative study featuring interviews of seven undocumented parents recruited at non-governmental clinics, three nurses at Child Health Centers, and information from key stakeholders retrieved at workshops as part of the TIP process. RESULTS: The content analysis revealed two main themes: parental fear of being questioned and parental acceptance of child immunization. Undocumented parents had a positive view and attitude toward childhood immunization but expressed strong fear of being asked for identification papers at healthcare facilities. Owing to lack of knowledge on entitlements of the undocumented among health personnel, parents were incorrectly rejected when seeking care for their children. Frequent mobility among undocumented may limit access to complete the immunization schedule. Undocumented parents mistrust healthcare providers and avoid health facilities, further delaying childrens' access to health care, including immunization services. CONCLUSIONS: The findings of this study confirm the complexity of barriers that undocumented parents face regarding childhood immunization. The TIP guide offers a valuable process for a deeper understanding of the determinants of immunization challenges among undocumented migrants.

Opportunistic virus DNA levels after pediatric stem cell transplantation: serostatus matching, anti-thymocyte globulin, and total body irradiation are additive risk factors.

Viral opportunistic infections remain a threat to survival after stem cell transplantation (SCT). We retrospectively investigated infections caused by cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus type 6 (HHV6), or adenovirus (AdV) during the first 6-12 months after pediatric SCT. Serum samples from 47 consecutive patients were analyzed by quantitative real-time polymerase chain reaction assay. DNAemia at any time point occurred for CMV in 47%, for EBV in 45%, for HHV6 in 28%, and for AdV in 28%. Three patients (6.3%) died of CMV-, EBV-, or AdV-related complications 4, 9, and 24 weeks after SCT, respectively, representing 21% of total mortality. These 3 cases were clearly distinguishable by DNAemia increasing to high levels. Serum positivity for CMV immunoglobulin G in either recipient or donor at the time of SCT, total body irradiation, and anti-thymocyte globulin conditioning were independent risk factors for high CMV or EBV DNA levels. We conclude that DNAemia levels help to distinguish significant viral infections, and that surveillance and prophylactic measures should be focused on patients with risk factors in whom viral complications rapidly can become fatal.

Four novel coeliac disease regions replicated in an association study of a Swedish-Norwegian family cohort.

Recent genome-wide association studies have identified 1q31 (RGS1), 2q11-12 (IL18RAP), 3p21 (CCR1/CCR3/CCR2), 3q25-26 (IL12A/SCHIP1), 3q28 (LPP), 4q27 (IL2/IL21), 6q25 (TAGAP) and 12q24 (SH2B3) as susceptibility regions for coeliac disease (CD). We have earlier replicated association with the IL2/IL21 region. This study aimed at replicating the remaining regions in a family cohort using the transmission disequilibrium test, which is not prone to population stratification as a source of false-positive results. Nine single nucleotide polymorphisms (SNPs) within these regions were genotyped in 325 Swedish-Norwegian CD families. We found significant associations with the same alleles in the regions 1q31 (rs2816316; P(nc)=0.0060), 3p21 (rs6441961; P(nc)=0.0006), 3q25-26 (rs17810564; P(nc)=0.0316 and rs9811792; P(nc)=0.0434) and 3q28 (rs1464510; P(nc)=0.0037). Borderline, but non-significant, associations were found for rs917997 (IL18RAP), whereas no evidence for association could be obtained for rs13015714 (IL18RAP) or rs1738074 (TAGAP). The lack of replication of the latter SNPs could be because of limited power. rs3184504 (SH2B3) was not analysed because of assay failure. The most significantly associated region, 3p21 (CCR1/CCR3/CCR2), was further analysed by typing of 30 SNPs, with the aim of identifying the causal variant responsible for the initial association. Several SNPs showed association with CD, but none displayed associations stronger than rs6441961, nor did any of them add to the effect initially marked by rs6441961 in a conditional analysis. However, differential effects of rs6441961(*)C carrying haplotypes were indicated, and we thus cannot exclude the possibility that our inability to obtain evidence for multiple independent effects in the CCR1/CCR3/CCR2 gene region was related to a power issue.

Association study of IL2/IL21 and FcgRIIa: significant association with the IL2/IL21 region in Scandinavian coeliac disease families.

The first genome-wide association study performed in a UK coeliac disease (CD) case-control cohort revealed association with a linkage disequilibrium block containing the KIAA1109/Tenr/IL2/IL21 genes. Also recently, an association with a non-synonymous polymorphism in FcgammaRIIa (CD32a) was reported in CD with an unusually strong P-value. We aimed to replicate the reported associations with the single nucleotide polymorphisms rs13119723 A>G and rs6822844 G>T in the KIAA1109/Tenr/IL2/IL21 region and rs1801274 G>A in the FcgammaRIIa gene in a family sample consisting of 325 Swedish/Norwegian families using the robust transmission disequilibrium test. The family sample used in this study included 100 families with two or more children affected by CD and 225 families with one affected child. We could confirm significant association between the polymorphisms rs13119723 A>G and rs6822844 G>T located in the KIAA1109/Tenr/IL2/IL21 region and CD (P-value 0.001 and 0.002, respectively). However, we found no association with the FcgammaRIIa rs1801274 G>A polymorphism (P-value=0.3). In conclusion, our results support the KIAA1109/Tenr/IL2/IL21 region as a true CD susceptibility region.

Genome-wide linkage analysis of Scandinavian affected sib-pairs supports presence of susceptibility loci for celiac disease on chromosomes 5 and 11.

Celiac disease (CD) is a common chronic inflammatory disorder of the small intestine with a multifactorial aetiology. HLA is a well-known risk factor, but other genetic factors also influence disease susceptibility. To identify the genes involved in this disorder, we performed a genome-wide scan on 106 well-defined Swedish and Norwegian families with at least two affected siblings. We investigated familial segregation of 398 microsatellite markers, and utilised non-parametric linkage analysis. The strongest linkage with disease was found to the HLA locus (6p) (P<0.000006). There were eight regions besides HLA with a point wise P value below 0.05. Among these eight regions were 11q and 5q, both of which have been suggested in several linkage studies of independent celiac disease families. We also performed a stratification analysis of families according to their HLA genotypes. This resulted in significant differences on chromosome 2q. These results indicate that 11q, 5q and possibly also 2q are true susceptibility regions in CD.

Paediatric aspects of coeliac disease: old challenges and new ones...

The concept of coeliac disease has expanded from a gastrointestinal disease with malabsorption to a systemic immunological disease with a genetic basis. Epidemiological studies indicate that environmental factors, like the infant feeding pattern, affect the clinical presentation while population-screening studies indicate that the prevalence, at least in Caucasian populations, is similar. Secondary complications, like malignancies, osteopenia - osteoporosis, gynaecological and obstetrical problems and autoimmune diseases, are common. The risk is reduced or prevented by treatment with a gluten-free diet. The basis for such a secondary prevention is: 1. early case-finding by a) knowledge about different presentations of the disease and factors affecting that, b) generous serological testing in patients with vague symptoms, c) screening of risk groups, and, 2. support for children and adolescents with coeliac disease to comply with the gluten-free diet.

[Proposed criteria for diagnosis of celiac disease in children]. / Förslag till kriterier för celiakidiagnos hos barn.

At a seminar arranged in September 1997 by the Swedish Paediatric Working Group for Coeliac Disease, a diagnostic protocol proposed by the working group was approved by a majority of the paediatricians present, representing almost all paediatric units in Sweden. Briefly, a small bowel biopsy is called for in all children, both at presentation and as a control during gluten-free dieting. Subsequent gluten challenge and biopsy are mandatory only in cases of atypical presentation or if the diagnosis is questioned at some future date. Serum antigliadin and anti-endomysial antibody tests are complementary tools. Agreement was also reached regarding the institution of a national coeliac disease registry.

Fine mapping study in Scandinavian families suggests association between coeliac disease and haplotypes in chromosome region 5q32.

The previous genome-wide scan in Scandinavian families supported earlier evidence for linkage of a region on chromosome 5 (5q31-33) to coeliac disease. This study deals with further genetic mapping of an 18 cM region, spanning from marker GAh18A (131.87 Mb) to D5S640 (149.96 Mb). Linkage and association analyses were performed in a two-step approach. First, seven microsatellites were added. Strong evidence for linkage was obtained with a Zlr score of 3.96, P(nc) = 4 x 10(-5) at marker D5S436. The strongest association was with a haplotype consisting of the markers D5S2033 and D5S2490 (P(nc) < 0.001). In the second step, we added 17 microsatellites and 69 single nucleotide polymorphisms (SNPs) to the analysis. These markers were located close to or within candidate genes across the region of approximately 7 Mb beneath the linkage peak marked by D5S2017 and D5S812. A substantial increase of the linkage signal with a maximum Zlr score of 4.6 at marker rs1972644 (P(nc) = 2 x 10(-6)) was obtained and several SNPs showed association. Seven SNPs that individually showed the strongest association were genotyped in a second independent family sample set (225 trios). In the trio family sample as well as in the multiplex family sample, the strongest association was found with SNPs within the region flanked by the associated microsatellites D5S2033 and D5S2490 at 5q32.

Characterization of the humoral immune response in two paediatric patients transplanted with split livers from ABO-incompatible living-related donors: appearance of cytomegalovirus-induced ABO antibodies.

Two blood group O paediatric patients, 12 and 6 months old, were transplanted with liver segments from their blood group A2Le (a(-)b+) Se and blood group A1Le (a(-)b+) Se fathers, respectively. Recipient anti-A antibody titres were reduced prior to transplantation by blood exchange. Both patients had rejection episodes in the post-transplant period that were reversed by anti-rejection therapy. No anti-A antibody titre rise occurred concomitant with these rejections. Postoperatively both patients had cytomegalovirus (CMV) infections, and simultaneous with these infections, a strong increase in anti-A antibody titres was seen, but no rejection occurred. The anti-A antibody titre increase seemed to be specific for A antigens, because the anti-B and anti-alphaGal (anti-pig) antibody titres did not show any changes. CMV infection is a serious cause of morbidity and mortality in immunosuppressed patients, and the virus can influence glycosylation of infected cells. Whether this can explain the importance of the infection in relation to the increase in titre remains to be elucidated.

Liver transplantation--the first 25 years.

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Drs Homer A. Boushey, Professor of Medicine, and David G. Warnock, Associate Professor of Medicine, under the direction of Dr Lloyd H. Smith, Jr, Professor of Medicine and Associate Dean in the School of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143.

A new laboratory kit for anti-gliadin IgA at diagnosis and follow-up of childhood celiac disease.

A new laboratory kit measuring anti-gliadin IgA level by enzyme immunoassay has been evaluated to assess the test's potential for screening children with suspected celiac disease for small intestinal biopsy and predicting mucosal relapse after gluten challenge. One hundred thirty children were tested, and the results were related to the histopathologic findings of the intestinal mucosa and the final diagnosis. The sensitivity of the test was 97% and the specificity was 92% in the studied population. Forty-five children with celiac disease on different diets were observed. All had reduced anti-gliadin IgA levels on a gluten-free diet, and 91% had normal levels after 1 year. Two of four patients with increased values had an insufficient diet. During gluten challenge, 38 of 45 children showed increased anti-gliadin IgA levels. Of the remaining seven, five reacted either with immediate and strong symptoms or had spontaneously reduced gluten intake, or had an acquired IgA deficiency. In two cases, there was no explanation. In five children without relapse on gluten challenge, the anti-gliadin IgA level remained normal. Provided that IgA deficiency is ruled out and the gluten intake is sufficient, the test is reliable for screening and has a potential to replace the third biopsy.