Improved anamnestic response among adolescents boosted with a higher dose of the hepatitis B vaccine.

Some hepatitis B vaccine booster studies have suggested waning of vaccine-induced immunity in adolescents vaccinated starting at birth. Those studies, however, used a pediatric formulation of the hepatitis B vaccine as a booster to detect anamnestic response. We compared adolescents boosted with an adult dose of hepatitis B vaccine with those boosted with a pediatric dose. Among adolescents who had lost protective antibody levels against hepatitis B, a higher proportion had an anamnestic response when boosted with the adult dose (60.0% vs. 43.8%). Thus, higher antigen concentrations may be required to elicit an adequate immune memory response. Despite improved anamnestic response, our study still raises concerns about whether children immunized in early infancy will remain protected from hepatitis B as they age into adulthood.

Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.

It has been argued that the limited genetic diversity and reduced allelic heterogeneity observed in isolated founder populations facilitates discovery of loci contributing to both Mendelian and complex disease. A strong founder effect, severe isolation, and substantial inbreeding have dramatically reduced genetic diversity in natives from the island of Kosrae, Federated States of Micronesia, who exhibit a high prevalence of obesity and other metabolic disorders. We hypothesized that genetic drift and possibly natural selection on Kosrae might have increased the frequency of previously rare genetic variants with relatively large effects, making these alleles readily detectable in genome-wide association analysis. However, mapping in large, inbred cohorts introduces analytic challenges, as extensive relatedness between subjects violates the assumptions of independence upon which traditional association test statistics are based. We performed genome-wide association analysis for 15 quantitative traits in 2,906 members of the Kosrae population, using novel approaches to manage the extreme relatedness in the sample. As positive controls, we observe association to known loci for plasma cholesterol, triglycerides, and C-reactive protein and to a compelling candidate loci for thyroid stimulating hormone and fasting plasma glucose. We show that our study is well powered to detect common alleles explaining >/=5% phenotypic variance. However, no such large effects were observed with genome-wide significance, arguing that even in such a severely inbred population, common alleles typically have modest effects. Finally, we show that a majority of common variants discovered in Caucasians have indistinguishable effect sizes on Kosrae, despite the major differences in population genetics and environment.

Persistence of protection against hepatitis B virus infection among adolescents vaccinated with recombinant hepatitis B vaccine beginning at birth: a 15-year follow-up study.

BACKGROUND: Long-term follow-up studies of populations that received recombinant hepatitis B (HB) vaccination beginning at birth are limited. METHODS: Micronesian adolescents who had received 3 doses of recombinant HB vaccine (Recombivax 5 microg at birth, 2.5 microg at 2 months, 2.5 microg ug at 6 months) and tested negative for antibody to HB core antigen (anti-HBc) 2 years after primary vaccination (baseline testing) were followed up 15 years after primary vaccination. After testing for anti-HBc, HB surface antigen (HBsAg), and antibody to HBsAg (anti-HBs), participants received a booster dose of HB vaccine. An anamnestic response was defined as an increase in anti-HBs concentrations to a level > or = 10 mIU/mL 14 days postbooster. RESULTS: Of the 105 participants, 42 (40.0%) had anti-HBs concentrations > or = 10 mIU/mL on baseline testing. At 15 years, 8 (7.6%) were anti-HBc positive; none were HBsAg positive. Of the remaining 97, 7 (7.3%) had anti-HBs concentrations > or = 10 mIU/mL. Of the 96 who received a booster dose, 46 (47.9%) had an anamnestic response; final antibody concentrations were 10-99 mIU/mL for 17 (17.7%) and > 100 mIU/mL for 29 (30.2%). Participants with anti-HBs concentrations > or = 10 mIU/mL on baseline testing were more likely to have an anamnestic response at 15 years [26/39 (66.7%) versus 20/57 (35.1%); P = 0.003]. CONCLUSIONS: Fifteen years after primary vaccination starting at birth, 8% of participants had evidence of past HB virus infection, but none had chronic infection. Absence of an anamnestic response to an additional vaccine dose, seen in half of participants, might indicate waning immunity.

Linkage analysis of quantitative traits for obesity, diabetes, hypertension, and dyslipidemia on the island of Kosrae, Federated States of Micronesia.

Obesity, diabetes, hypertension, and heart disease are highly heritable conditions that in aggregate are the major causes of morbidity and mortality in the developed world and are growing problems in developing countries. To map the causal genes, we conducted a population screen for these conditions on the Pacific Island of Kosrae. Family history and genetic data were used to construct a pedigree for the island. Analysis of the pedigree showed highly significant heritability for the metabolic traits under study. DNA samples from 2,188 participants were genotyped with 405 microsatellite markers with an average intermarker distance of 11 cM. A protocol using loki, a Markov chain Monte Carlo sampling method, was developed to analyze the Kosraen pedigree for height, a model quantitative trait. Robust quantitative trait loci for height were found on 10q21 and 1p31. This protocol was used to map a set of metabolic traits, including plasma leptin to chromosome region 5q35; systolic blood pressure to 20p12; total cholesterol to 19p13, 12q24, and 16qter; hip circumference to 10q25 and 4q23; body mass index to 18p11 and 20q13; apolipoprotein B to 2p24-25; weight to 18q21; and fasting blood sugar to 1q31-1q43. Several of these same chromosomal regions have been identified in previous studies validating the use of loki. These studies add information about the genetics of the metabolic syndrome and establish an analytical approach for linkage analysis of complex pedigrees. These results also lay the foundation for whole genome scans with dense sets of SNPs aimed to identifying causal genes.

High prevalence of overweight among pediatric users of community health centers.

OBJECTIVE: With the increasing prevalence of pediatric obesity, it is important to identify high-risk populations of children to direct limited resources for prevention and treatment to those who are most vulnerable. The objectives of this study were to determine the prevalence of overweight in children who are clients of community health centers in medically underserved areas of the Health Resources and Service Administration regions II and III (Mid-Atlantic and Puerto Rico), compare this prevalence to nationally representative data, and contrast prevalence data between geographic areas and racial/ethnic groups. METHODS: The charts from a representative sample of 2474 children using 30 community health centers in 2001 were abstracted to collect clinically measured weight and height. Overweight was defined as a body mass index of > or =95th percentile of a reference population. To generate an unbiased estimate of overweight, multiple imputations were used for missing data. These data were compared with the 1999-2002 National Health and Nutrition Examination Survey. RESULTS: The prevalence of overweight was elevated in this sample of children aged 2 to 5 years (21.8%; 95% confidence interval [CI]: 19.1-24.8) and 6 to 11 years (23.8%; 95% CI: 16.9-27.7) compared with the 1999-2002 National Health and Nutrition Examination Survey (10.3% and 15.8%, respectively). No significant differences in prevalence were observed between Asian American (18.2%; 95% CI: 11.2-28.3), Hispanic (24.6%; 95% CI: 21.3-28.2), non-Hispanic black (25.6%; 95% CI: 20.8-30.9), and non-Hispanic white (22.8%; 95% CI: 19.0-27.0) children. Furthermore, no differences in prevalence were observed between children using community health centers in continental urban (23.7%; 95% CI: 20.6-27.2), suburban (24.0%; 95% CI: 20.0-28.5), or rural (22.9%; 95% CI: 19.3-26.9) areas. CONCLUSIONS: The present study identified a population of children at particularly high risk for obesity based on the type of health care delivery system they use regardless of race/ethnicity or geographic characteristics. Because community health centers are experienced in prevention and serve >4.7 million children in the United States, they may be a particularly promising point of access and setting for pediatric obesity prevention.

Risk factors for vitamin A deficiency among preschool aged children in Pohnpei, Federated States of Micronesia.

In 1993, the Department of Health of the Federated States of Micronesia (FSM) conducted a population-based stratified random survey among 355 children aged 24-48 months in Pohnpei, one of the four FSM States. The objective was to determine the prevalence, and explore risk factors for vitamin A deficiency (VAD). Trained field workers collected data from a range of demographic, dietary and socioeconomic variables related to the children. The serum retinol concentration was 19.4 +/- 7.5 microg/dl (mean +/- SD), and the VAD prevalence (serum retinol <20 microg/dl) 53.1 per cent. The significant independent risk factors, determined by logistic regression, were: mother's work at home, sibling <2 years older, rural household located on the main island, early weaning, and child anemia, controlling for pipe water and electricity in the household. If compared with a reference of apparently healthy children of similar age in the USA, the distribution of serum retinol among young Pohnpei children was shifted entirely to low levels. We conclude that eliminating the pervasive VAD problem in Pohnpei would require a multi-pronged tactical approach that combines dietary improvement strategies with the ongoing supplementation effort.