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Background: Alaska Native (AN) infants are at risk for severe disease due to respiratory syncytial virus (RSV) and influenza. Maternal immunization protects young infants through transplacental antibody transfer. RSV- and influenza-specific transplacental antibody transfer in mother-infant pairs has not previously been evaluated in the AN population., Methods: Serum samples collected during pregnancy and at birth from AN mother-infant pairs in the Yukon-Kuskokwim Delta region (YKD) of Alaska (2000-2011; n = 75) and predominantly white pairs in Seattle, Washington (2014-2016; n = 57), were tested for RSV and influenza antibody using a microneutralization and hemagglutination inhibition assay, respectively, and compared between sites., Results: Mean RSV antibody concentrations in pregnant women in YKD and Seattle were similar (log2 RSV antibody 10.6 vs 10.7, P = .86), but cord blood RSV antibody concentrations were significantly lower in infants born to mothers in YKD compared with Seattle (log2 RSV antibody 11.0 vs 12.2, P < .001). Maternal and cord blood influenza antibody concentrations were lower for women and infants in YKD compared with Seattle for all 4 influenza antigens tested (all P < .05). The mean cord to maternal RSV antibody transfer ratio was 1.15 (standard deviation [SD], 0.13) in mother-infant pairs in Seattle compared with 1.04 (SD, 0.08) in YKD. Mean cord blood to maternal antibody transfer ratios for influenza antigens ranged from 1.22 to 1.42 in Seattle and from 1.05 to 1.59 in YKD., Conclusions: Though the transplacental antibody transfer ratio was high (>1.0) for both groups, transfer ratios for RSV antibody were significantly lower in AN mother-infant pairs. Further studies are needed to elucidate the impact of lower transplacental antibody transfer on infant disease risk in rural Alaska.Alaska Native and continental US mother-infant pairs have high transplacental antibody transfer ratios (>1.0) for influenza and respiratory syncytial virus, but anti-respiratory syncytial virus antibody levels are significantly lower in Alaska Native pairs than in those from the continental US., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In Alaska, while introduction of 13-valent pneumococcal conjugate vaccine led to declines in invasive pneumococcal disease, carriage prevalence remained stable because of replacement with non-vaccine serotypes. We assessed antibiotic non-susceptibility of carried pneumococci during serotype redistribution, determined the contributions of within-serotype shifts, and assessed factors that could explain changes in non-susceptibility., Methods: Each year from 2008 to 2015, at multiple sites in Alaska, we collected nasopharyngeal swabs and completed surveys for a convenience sample of participants. Pneumococcal serotyping and antimicrobial susceptibility testing for penicillin and erythromycin were performed. We described changes in non-susceptibility of isolates from 2008-2011 to 2012-2015, and assessed the contributions of serotype redistribution and within-serotype changes in non-susceptibility by comparing observed data to modeled data removing either factor. We used weighted logistic regression to assess whether reported risk factors could explain changes over time in non-susceptibility within serotypes., Results: From 2008-2011 to 2012-2015, the overall proportion of isolates non-susceptible to penicillin or erythromycin increased by 3%, from 23% (n = 1,183) to 26% (n = 1,589; P < 0.05). However, a decrease of 3% would be expected if serotype redistribution occurred without within-serotype changes in non-susceptibility. Standardization by either factor produced hypothetical data significantly different to observed data. Within serotypes, the average annual increase in odds of non-susceptibility to penicillin or erythromycin was 1.08 (95% CI 1.05-1.11). Recent antibiotic exposure, urban residence and increased household size of participants predicted isolate non-susceptibility but did not explain the increase over time., Discussion: An overall increase in non-susceptibility of carried pneumococcal isolates to penicillin or erythromycin resulted from increases in non-susceptibility within serotypes, which outweighed a protective effect of serotype redistribution. Characterization of emerging resistant clones within carried non-vaccine serotypes, including risk factors for colonization and disease, would support disease prevention efforts and inform vaccine strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Objectives: Burden of pneumococcal disease depends on the prevalence and invasive disease potential of serotypes. We aimed to estimate the invasive disease potential of serotypes in children under 5 years of age by combining data from different settings with routine immunisation with pneumococcal conjugate vaccines (PCV)., Methods: We conducted a systematic review, supplemented by unpublished data, to identify data on the frequency of pneumococcal serotypes in carriage and invasive pneumococcal disease (IPD). We estimated the invasive disease potential of serotypes as the ratio of IPD in relation to carriage (odds ratio and 95%CI) compared with 19A (reference serotype) by meta-analysis. We report results based on a random effects model for children aged 0-23, 24-29, and 0-59 months and by invasive clinical syndromes., Results: In comparison with 19A, serotypes 1, 7F, and 12F had a significantly higher invasive disease potential in children aged 0-23 and 0-59 months for all IPD and clinical syndromes (OR > 5). Several non-vaccine types (NVTs) (6C, 15A, 15BC, 16F, 23B, in these two age groups) had a lower invasive disease potential than 19A (OR 0.1-0.3). NVTs 8, 12F, 24F, and 33F were at the upper end of the invasiveness spectrum., Conclusions: There is substantial variation among pneumococcal serotypes in their potential to cause IPD and disease presentation, which is influenced by age and time after PCV introduction. Surveillance of IPD and carriage is critical to understand the expected effectiveness of current PCVs (in the longer term) and guide the development of future vaccines., (Copyright © 2018 The British Infection Association. All rights reserved.)

Background: Helicobacter pylori is one of the most common human infections in the world, and studies in Alaska Native people, as well as other Indigenous peoples, have shown a high prevalence of this gastric infection. This study was undertaken to determine the prevalence of H. pylori infection by urea breath test (UBT) and anti- H. pylori IgG among Alaskans living in four regions of the state and to identify factors associated with infection., Methods: A convenience sample of persons > 6 months old living in five rural and one urban Alaskan community were recruited from 1996 to 1997. Participants were asked about factors possibly associated with infection. Sera were collected and tested for anti- H. pylori IgG antibodies; a UBT was administered to participants > 5 years old., Results: We recruited 710 people of whom 571 (80%) were Alaska Native and 467 (66%) were from rural communities. Rural residents were more likely to be Alaska Native compared with urban residents (P < .001). Of the 710 people, 699 (98%) had a serum sample analyzed, and 634 (97%) persons > 5 years old had a UBT performed. H. pylori prevalence was 69% by UBT and 68% by anti- H. pylori IgG. Among those with a result for both tests, there was 94% concordance. Factors associated with H. pylori positivity were Alaska Native racial status, age ≥ 20 years, rural region of residence, living in a crowded home, and drinking water that was not piped or delivered., Conclusions: Helicobacter pylori prevalence is high in Alaska, especially in Alaska Native persons and rural residents. Concordance between UBT and serology was also high in this group. Two socioeconomic factors, crowding and drinking water that was not piped or delivered, were found to be associated with H. pylori positivity., (© 2018 John Wiley & Sons Ltd.)

Objective: To measure the trends in traditional marine food intake and serum vitamin D levels in Alaska Native women of childbearing age (20-29 years old) from the 1960s to the present., Design: We measured a biomarker of traditional food intake, the δ15N value, and vitamin D level, as 25-hydroxycholecalciferol (25(OH)D3) concentration, in 100 serum samples from 20-29-year-old women archived in the Alaska Area Specimen Bank, selecting twenty-five per decade from the 1960s to the 1990s. We compared these with measurements of red-blood-cell δ15N values and serum 25(OH)D3 concentrations from 20-29-year-old women from the same region collected during the 2000s and 2010s in a Center for Alaska Native Health Research study., Setting: The Yukon Kuskokwim Delta region of south-west Alaska., Subjects: Alaska Native women (n 319) aged 20-29 years at the time of specimen collection., Results: Intake of traditional marine foods, as measured by serum δ15N values, decreased significantly each decade from the 1960s through the 1990s, then remained constant from the 1990s through the present (F 5,306=77·4, P<0·0001). Serum vitamin D concentrations also decreased from the 1960s to the present (F 4,162=26·1, P<0·0001)., Conclusions: Consumption of traditional marine foods by young Alaska Native women dropped significantly between the 1960s and the 1990s and was associated with a significant decline in serum vitamin D concentrations. Studies are needed to evaluate the promotion of traditional marine foods and routine vitamin D supplementation during pregnancy for this population.

Objectives: To evaluate the hepatocellular carcinoma (HCC) risk in Alaska Native children and young adults with hepatitis B virus (HBV)., Study Design: Retrospective analysis of a population-based cohort of Alaska Native persons with HBV followed during 1982-2012. All individuals with HBV were offered HCC screening regardless of age using alpha-fetoprotein every 6 months; persons with an elevated alpha-fetoprotein or persons at high-risk for HCC, such as cirrhosis, family history of HCC, were offered ultrasound. We calculated the HCC incidence/1000 person-years from date of cohort entry until death, diagnosis of HCC, or attaining the age of 40 years (males) or 50 years (females)., Results: We followed 1083 subjects with HBV (56% male) comprising 5 genotypes (A2 [12.5%], B6 [1.7%], C [5.3%], D [49.7%], F1 [18.6%], unknown [12.4%]) for a median of 23.4 years/person. We observed 22 HCC cases (incidence/1000 person-years follow-up: 1.0); 19 HCC cases among persons with genotype F1. There was no significant difference in HCC incidence between males (1.4) and females (0.6). The HCC incidence was significantly higher for persons with genotype F1 (4.4) compared with genotype A2 (0.4) and D (0.2) and remained higher among persons with HBV genotype F1 excluding persons with HCC family history/cirrhosis (1.9)., Conclusions: Alaska Native children and young adults with HBV genotype F1 are at high risk for HCC and should receive HCC surveillance. For males <40 years of age and females <50 years of age with HBV in regions of the world with a high genotype F prevalence, testing/confirming genotype F can identify persons who could benefit from HCC surveillance., Competing Interests: None of the authors have any conflicts to disclose. No honoraria, grants, or other forms of payment were given to any of the authors to produce the manuscript., (Published by Elsevier Inc.)

Here we describe the relationships between serotypes, genotypes, and antimicrobial susceptibility among isolates causing invasive pneumococcal disease in Alaskan children during the pneumococcal conjugate vaccine (PCV) era. From 2001 to 2013 we received 271 isolates representing 33 serotypes. The most common serotypes were 19A (29.5%, n= 80), 7F (12.5%, n= 34), 15B/C (6.3%, n= 17), and 22F (4.8%, n= 13). Multilocus sequence typing identified 11 clonal complexes (CC) and 45 singletons. Five CCs accounted for 52% (141/271) of the total: CC199 (21% [n= 57], serotypes 19A, 15B/C), CC191 (12.2% [n= 33], serotype 7F), CC172 (10.3% [n= 28], serotypes 19A, 23A, 23B), CC433 (4.4% [n= 12], serotype 22F), and CC100 (4.4% [n= 12], serotype 33F). The proportion of isolates nonsusceptible to erythromycin and tetracycline increased after 13-valent PCV use (14% [n= 30] versus 29% [n= 14]; P= 0.010) and (4% [n= 9] versus 22% [n= 11]; P< 0.001), respectively. The genetic diversity also increased after 13-valent PCV use (Simpson's diversity index =0.95 versus 0.91; P= 0.022)., (Published by Elsevier Inc.)

Background: The American Association for the Study of Liver Diseases (AASLD) recommends semi-annual hepatocellular carcinoma (HCC) screening using ultrasound (US) in persons with chronic hepatitis B (CHB) virus infection at high risk for HCC such as Asian males aged ≥40 years and Asian females aged ≥50 years., Objective: To analyse the cost-effectiveness of 2 HCC screening methods in the Alaska Native (AN) health system: US-alone, or screening by alpha-fetoprotein (AFP) initially and switching to US for subsequent screenings if AFP >10 ng/mL (AFP→US)., Design: A spreadsheet-based model was developed for accounting the costs of 2 hypothetical HCC screening methods. We used epidemiologic data from a cohort of 839 AN persons with CHB who were offered HCC screening by AFP/US semi-annually during 1983-2012. We assumed that compared with AFP→US, US-alone identifies 33% more tumours at an early stage (defined as a single tumour ≤5 cm or ≤3 tumours ≤3 cm in diameter). Years of life gained (YLG) attributed to screening was estimated by comparing additional years of survival among persons with early- compared with late-stage tumours. Screening costs were calculated using Medicare reimbursement rates in 2012. Future screening costs and YLG were projected over a 30-year time horizon using a 3% discount rate., Results: The total cost of screening for the cohort by AFP→US would have been approximately $357,000 ($36,000/early-stage tumour detected) compared to $814,000 ($59,000/early-stage tumour detected) by US-alone. The AFP→US method would have yielded an additional 27.8 YLG ($13,000/YLG) compared with 38.9 YLG ($21,000/YLG) for US-alone. Screening by US-alone would incur an additional $114,000 per extra early-tumour detected compared with AFP→US and $41,000 per extra YLG., Conclusions: Although US-alone HCC screening might have yielded more YLG than AFP→US, the reduced costs of the AFP→US method could expand access to HCC screening in resource constrained settings.

Unlabelled: The effect of passively transferred maternal antibody to hepatitis A virus (anti-HAV) on the duration of seropositivity after hepatitis A vaccination during infancy and early childhood is unclear. We obtained levels of anti-HAV at intervals through age 15-16 years among three groups of Alaskan Native children who initiated a two-dose inactivated hepatitis A vaccination series at ages 6 months (group 1), 12 months (group 2), and 15 months (group 3), each group randomized according to maternal anti-HAV status. Seropositivity (anti-HAV ≥20 mIU/mL) 30 years after the second vaccine dose among the three groups was predicted using a random effects model. One hundred eighty-three children participated in the study; follow-up did not differ significantly by vaccine group or maternal anti-HAV status. Although the frequency of seropositivity among all participants through age 10 years was high (100% among groups 2 and 3 and >90% among group 1), there was a decrease thereafter through age 15-16 years among group 1 children, who initiated vaccination at age 6 months (50%-75%), and among maternal anti-HAV-positive children in groups 2 and 3 (67%-87%), who initiated vaccination at ages 12 months and 15 months, respectively. Nonetheless, the model indicated that anti-HAV seropositivity should persist for ≥30 years after vaccination in 64% of all participants; among those seropositive at age 15-16 years, 84% were predicted to remain so for ≥30 years., Conclusion: Most children vaccinated during early childhood available for sampling maintained seropositivity through age 15-16 years; however, seropositivity was less frequent among those starting vaccination at age 6 months and among maternal antibody-positive participants who started vaccination at age 12 months or 15 months; overall, our findings support current vaccine recommendations and continued follow-up of this cohort., (© 2015 by the American Association for the Study of Liver Diseases. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Community-acquired methicillin-resistant Staphylococcus aureus and methicillin-sensitive S. aureus infections are common to south-western Alaska and have been associated with traditional steambaths. More than a decade ago, recommendations were made to affected communities that included preventive skin care, cleaning methods for steambath surfaces, and the use of protective barriers while in steambaths to reduce the risk of S. aureus infection., Objective: A review of community medical data suggested that the number of skin infection clinical encounters has increased steadily over the last 3 years and we designed a public health investigation to seek root causes., Study Design: Using a mixed methods approach with in-person surveys, a convenience sample (n=492) from 3 rural communities assessed the range of knowledge, attitudes and practices concerning skin infections, skin infection education messaging, prevention activities and home self-care of skin infections., Results: We described barriers to implementing previous recommendations and evaluated the acceptability of potential interventions. Prior public health messages appear to have been effective in reaching community members and appear to have been understood and accepted. We found no major misconceptions regarding what a boil was or how someone got one. Overall, respondents seemed concerned about boils as a health problem and reported that they were motivated to prevent boils. We identified current practices used to avoid skin infections, such as the disinfection of steambaths. We also identified barriers to engaging in protective behaviours, such as lack of access to laundry facilities., Conclusions: These findings can be used to help guide public health strategic planning and identify appropriate evidence-based interventions tailored to the specific needs of the region.

Background: Respiratory syncytial virus (RSV) is the most common pathogen identified in young children with acute lower respiratory infection (ALRI) as well as an important cause of hospital admission. The high incidence of RSV infection and its potential severe outcome make it important to identify and prioritise children who are at higher risk of developing RSV-associated ALRI. We aimed to identify risk factors for RSV-associated ALRI in young children., Methods: We carried out a systematic literature review across 4 databases and obtained unpublished studies from RSV Global Epidemiology Network (RSV GEN) collaborators. Quality of all eligible studies was assessed according to modified GRADE criteria. We conducted meta-analyses to estimate odds ratios with 95% confidence intervals (CI) for individual risk factors., Results: We identified 20 studies (3 were unpublished data) with "good quality" that investigated 18 risk factors for RSV-associated ALRI in children younger than five years old. Among them, 8 risk factors were significantly associated with RSV-associated ALRI. The meta-estimates of their odds ratio (ORs) with corresponding 95% confidence intervals (CI) are prematurity 1.96 (95% CI 1.44-2.67), low birth weight 1.91 (95% CI 1.45-2.53), being male 1.23 (95% CI 1.13-1.33), having siblings 1.60 (95% CI 1.32-1.95), maternal smoking 1.36 (95% CI 1.24-1.50), history of atopy 1.47 (95% CI 1.16-1.87), no breastfeeding 2.24 (95% CI 1.56-3.20) and crowding 1.94 (95% CI 1.29-2.93). Although there were insufficient studies available to generate a meta-estimate for HIV, all articles (irrespective of quality scores) reported significant associations between HIV and RSV-associated ALRI., Conclusions: This study presents a comprehensive report of the strength of association between various socio-demographic risk factors and RSV-associated ALRI in young children. Some of these amenable risk factors are similar to those that have been identified for (all cause) ALRI and thus, in addition to the future impact of novel RSV vaccines, national action against ALRI risk factors as part of national control programmes can be expected to reduce burden of disease from RSV. Further research which identifies, accesses and analyses additional unpublished RSV data sets could further improve the precision of these estimates.

Background: Alaska Native infants from the Yukon-Kuskokwim Delta (YKD) experienced respiratory syncytial virus (RSV) hospitalization rates 5 times higher and an RSV season twice as long as the general US infant population. We describe trends in hospitalization rates and seasonality during 18 years of continuous RSV surveillance in this population and explore contributions of climate and sociodemographic factors., Methods: We abstracted clinical and RSV test information from computerized medical records at YKD Regional Hospital and Alaska Native Medical Center from 1994 to 2012 to determine hospitalization rates and RSV season timing. Descriptive village and weather data were acquired through the US Census and Alaska Climate Research Center, University of Alaska, Fairbanks, respectively., Results: During 1994-2012, YKD infant RSV hospitalization rates declined nearly 3-fold, from 177 to 65 per 1000 infants/yr. RSV season onset shifted later, from mid October to late December, contributing to a significantly decreased season duration, from 30 to 11 weeks. In a multivariate analysis, children from villages with more crowded households and lacking plumbed water had higher rates of RSV hospitalizations (relative rate, 1.17; P = 0.0005 and relative rate, 1.45; P = 0.0003). No association of temperature or dew point was found with the timing or severity of RSV season., Conclusions: Although the RSV hospitalization rate decreased 3-fold, YKD infants still experience a hospitalization rate 3-fold higher than the general US infant population. Overcrowding and lack of plumbed water were associated with RSV hospitalization. Dramatic changes occurred in RSV seasonality, not explained by changes in climate.

Hepatitis B antibody persistence was assessed in individuals who had previously received a vaccine booster. We measured hepatitis B surface antigen antibody (anti-HBs) levels 7 to 9 years post-hepatitis B booster in individuals with primary vaccination at birth. While 95 (91.3%) of 104 participants had detectable anti-HBs (minimum, 0.1 mIU/ml; maximum, 1,029 mIU/ml), only 43 (41%) had protective levels of ≥10 mIU/ml. Pre- and week 4 postbooster anti-HBs levels were significant predictors of hepatitis B immunity at follow-up (P < 0.001). Almost all participants had detectable anti-HBs 7 to 9 years after the hepatitis B vaccine booster, but less than half had levels ≥10 mIU/ml., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Background: Alaska Native persons experience gastric cancer incidence and mortality rates that are three to four times higher than in the general United States population., Objective: To evaluate pepsinogen I, pepsinogen I/II ratio, anti-Helicobacter pylori and cytotoxin-associated gene A (CagA) antibody levels, and blood group for their associations with gastric cancer development in Alaska Native people., Methods: The present analysis was a retrospective case-control study that matched gastric cancers reported to the Alaska Native Tumor Registry from 1969 to 2008 to three controls on known demographic risk factors for H pylori infection, using sera from the Alaska Area Specimen Bank. Conditional logistic regression evaluated associations between serum markers and gastric cancer., Results: A total of 122 gastric cancer cases were included, with sera predating cancer diagnosis (mean = 13 years) and 346 matched controls. One hundred twelve cases (91.8%) and 285 controls (82.4%) had evidence of previous or ongoing H pylori infection as measured by anti-H pylori antibody levels. Gastric cancer cases had a 2.63-fold increased odds of having positive anti-H pylori antibodies compared with their matched controls (P=0.01). In a multivariate model, noncardia gastric cancer (n=94) was associated with anti-H pylori antibodies (adjusted OR 3.92; P=0.004) and low pepsinogen I level (adjusted OR 6.04; P=0.04). No association between gastric cancer and blood group, anti-CagA antibodies or pepsinogen I/II ratio was found., Conclusion: Alaska Native people with gastric cancer had increased odds of previous H pylori infection. Low pepsinogen I level may function as a precancer marker for noncardia cancer.

Introduction: Recent epidemiologic research studies in rural Alaska have examined risk factors for infectious diseases collected at the household level. Examples include the health effects of in-home piped water and household air quality. Because the exposure is measured at the household level, it is necessary to determine if participants remained in the same house throughout the course of follow-up., Methods: We used data from a pneumococcal nasopharyngeal carriage study in 8 rural Alaska villages [3 regions; average number of persons: 642 (min 210, max 720 per village) to quantify changes in household membership and individual movements from 2008 to 2010. We define a household as a group of individuals living in a home together. Because the same households participated in carriage surveys over several years, we could determine changes on an annual basis. We calculated the percentage of households with a ≥ 1 person change in household members from year to year. Additionally, we present the percentage of individuals that changed households during consecutive years., Results: In 3 regions of Alaska, the average household size was 5 persons. Between 2008 and 2009, 50% (250/497) of households had a change in their membership (≥ 1 person in-migrated or out-migrated). Fifty-three percent of households experienced some migration of their members between 2009 and 2010. A total of 27 and 15% of households had a change of ≥ 2 and ≥ 3 persons, respectively. The percentage of households with movement was similar among the 3 rural regions and varied from 42 to 63% between villages. At the individual level, an average of 11% of persons changed households between years. The group with the most movement between houses was persons 18-29 years of age (19%), and least movement was in 5-10 and 50-64 years of age (6%). There was no difference in movement by gender., Conclusions: In rural Alaska, 52% of households experienced movement of members between years and 11% of individuals change households. These are important demographic figures to consider when planning and designing studies that measure an epidemiological exposure at the household level. Power and sample size calculations should account for the loss to follow-up associated with in- and out-migration of individuals from households.

Background: Hepatitis A is mostly a self-limiting disease but causes substantial economic burden. Consequently, United States Advisory Committee for Immunization Practices recommends inactivated hepatitis A vaccination for all children beginning at age 1 year and for high risk adults. The hepatitis A vaccine is highly effective but the duration of protection is unknown., Methods: We examined the proportion of children with protective hepatitis A antibody levels (anti-HAV ≥20 mIU/mL) as well as the geometric mean concentration (GMC) of anti-HAV in a cross sectional convenience sample of individuals aged 12-24 years, who had been vaccinated with a two-dose schedule in childhood, with the initial dose at least 5 years ago. We compared a subset of data from persons vaccinated with two-doses (720 EL.U.) at age 3-6 years with a demographically similar prospective cohort that received a three-dose (360 EL.U.) schedule and have been followed for 17 years., Results: No significant differences were observed when comparing GMC between the two cohorts at 10 (P=0.467), 12 (P=0.496), and 14 (P=0.175) years post-immunization. For the three-dose cohort, protective antibody levels remain for 17 years and have leveled-off over the past 7 years., Conclusion: The two- and three-dose schedules provide similar protection >14 years after vaccination, indicating a booster dose is not needed at this time. Plateauing anti-HAV GMC levels suggest protective antibody levels may persist long-term., (Published by Elsevier Ltd.)

Background: During 1996 to 2000, Alaska Native children aged <5 years from Yukon Kuskokwim Delta (YKD) had invasive pneumococcal disease (IPD) rates 10-fold higher than non-Alaska Native children (547/100,000/yr versus 56/100,000/yr). After 7-valent pneumococcal conjugate vaccine (PCV7) introduction, IPD rates decreased to 148 per 100,000 during 2001 to 2004, increasing to 426 per 100,000 during 2005 to 2007 due to non-vaccine serotype disease. In 2009, we evaluated safety, immunogenicity and impact of 13-valent PCV (PCV13) in YKD children., Methods: In a prelicensure open-label clinical trial, eligible YKD children aged <5 years were offered PCV13 as appropriate for age and prior PCV7 history. PCV13 impact was assessed using existing Alaska-wide IPD surveillance. Serotype-specific anti-pneumococcal IgG levels were measured postinfant series and posttoddler dose in a subset of subjects. Adverse events and serious adverse events were collected in all; local reactions and systemic events were collected in toddlers. All YKD children were offered licensed PCV13 when it became available., Results: Three hundred seventy-two subjects received PCV13 during the clinical trial and 3342 postlicensure (April 2010 to August 2011). Adverse events were typically mild, or generally consistent with common childhood illnesses. IgG levels following PCV13 were similar to other populations. In YKD children aged <5 years, 52 IPD cases (31 PCV13-serotype) occurred during 2005 to 2008 (399.0/100,000/yr) versus 9 (7 PCV13-serotype) during January 2009 to August 2011 (106.7/100,000/yr; P < 0.001). No PCV13-serotype cases occurred among PCV13 recipients (3680 person follow-up years)., Conclusions: PCV13-serotype IPD incidence declined significantly after PCV13 introduction. Although non-PCV13-serotype IPD also declined significantly, absence of PCV13-serotype IPD in children who received PCV13 suggests a protective vaccine effect.

The Centers for Disease Control and Prevention recommends hepatitis A virus (HAV) vaccination for all children at age 1 year and for high-risk adults. The vaccine is highly effective; however, protection duration is unknown. We report HAV antibody concentrations 17 years after childhood immunization, demonstrating that protective antibody levels remain and have stabilized over the past 7 years.

Unlabelled: Persistence of seropositivity conferred by hepatitis A vaccine administered to children <2 years of age is unknown and passively transferred maternal antibodies to hepatitis A virus (maternal anti-HAV) may lower the infant's immune response to the vaccine. One hundred ninety-seven infants and young children were randomized into three groups to receive a two-dose hepatitis A vaccine: group 1 at 6 and 12 months, group 2 at 12 and 18 months, and group 3 at 15 and 21 months of age. Within each group, infants were randomized by maternal anti-HAV status. Anti-HAV levels were measured at 1 and 6 months and at 3, 5, 7, and 10 years after the second dose of hepatitis A vaccination. Children in all groups had evidence of seroprotection (>10 mIU/mL) at 1 month after the second dose. At 10 years, all children retained seroprotective anti-HAV levels except for only 7% and 11% of children in group 1 born to anti-HAV-negative and anti-HAV-positive mothers, respectively, and 4% of group 3 children born to anti-HAV-negative mothers. At 10 years, children born to anti-HAV-negative mothers in group 3 had the highest geometric mean concentration (GMC) (97 mIU/mL; 95% confidence interval, 71-133 mIU/mL) and children born to anti-HAV-positive mothers in group 1 had the lowest GMC (29 mIU/mL; 95% confidence interval, 20-40 mIU/mL). Anti-HAV levels through 10 years of age correlated with initial peak anti-HAV levels (tested at 1 month after the second dose)., Conclusion: The seropositivity induced by hepatitis A vaccine given to children <2 years of age persists for at least 10 years regardless of presence of maternal anti-HAV., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Objective: Lower respiratory tract infections (LRTIs) are a major cause of morbidity for children worldwide and particularly for children from developing and indigenous populations. In this study, we evaluated risk factors for hospitalization with LRTI in a region in southwest Alaska., Methods: The study was conducted from October 1, 2006, to September 30, 2007, in the Yukon Kuskokwim Delta region of Alaska. Cases were recruited from children <3 years of age hospitalized with LRTI. Controls were recruited during visits to the surrounding communities in the region and matched posthoc to cases on the basis of subregion, season, and age. Parents were interviewed for potential risk factors, and medical records were reviewed. Participants had a nasopharyngeal swab sample taken for polymerase chain reaction (PCR) testing for a panel of respiratory viruses. Samples positive for respiratory syncytial virus, human metapneumovirus, or parainfluenza type 3 were quantitated by reverse transcriptase real-time quantitative PCR., Results: One hundred twenty-eight cases were matched to 186 controls. In a multivariable conditional logistic regression model, significantly (P < .05) increased risk of hospitalization was associated with medically high-risk status, having a woodstove in the house, being bottle fed, and vomiting after feeding; living in a house that had 2 or more rooms with sinks was a protective factor. Viral loads in hospitalized cases were significantly higher than those in controls, but a strict cutoff level was not observed., Conclusions: Several risk factors for LRTI hospitalization were identified in this high risk population. Some factors are amenable to environmental and behavioral interventions.

Unlabelled: Alaska Native people experience the highest rates of acute and chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) in the United States. We examined the effect of a universal newborn immunization with hepatitis B vaccine and mass population screening immunization program initiated in 1984 on rates of HBV and HCC in children 25 years later. During this time, the population of Alaska Native people grew from an estimated 75,000 to 130,000 persons. A surveillance system to detect acute HBV infection in Alaska Native facilities was established in 1981. Cases of HCC in children under 20 years of age were identified using a National Cancer Institute (NCI)-funded Cancer Registry established in 1969 coupled with an active surveillance program of screening persons with chronic HBV semiannually for alpha-fetoprotein since 1982. The incidence of acute symptomatic HBV infection in persons <20 years of age fell from cases 19/100,000 in 1981-1982 to 0/100,000 in 1993-1994. No cases of acute HBV have occurred in children since 1992. The incidence of HCC in persons <20 years decreased from 3/100,000 in 1984-1988 to zero in 1995-1999 and no cases have occurred since 1999. The number of identified hepatitis B surface antigen-positive children <20 years in the Alaska Native population declined from 657 in 1987 to two in 2008., Conclusion: Universal newborn vaccination coupled with mass screening and immunization of susceptible Alaska Natives has eliminated HCC and acute symptomatic HBV infection among Alaska Native children and this approach is the best way to prevent HBV-related disease in children., (Copyright © 2011 American Association for the Study of Liver Diseases.)

We analyzed hospitalizations for empyema among Alaska Native (AN) children and the general population of US children <10 years of age during the years 1998 to 2007. We also analyzed invasive pneumococcal disease in AN children. Between 1998 and 2000, the average annual hospitalization rate for empyema was higher for AN children (51.8 per 100,000/yr) than that for US children (24.2 [95% confidence interval: 20.4, 27.9] per 100,000/yr), and had increased in 2004-2007 in both populations (59.6 and 36.0 [95% confidence interval: 30.1, 41.8], respectively). Pneumococcal empyema increased in AN children despite a decrease in invasive pneumococcal disease pneumonia.

Background: Older adults are at highest risk of invasive pneumococcal disease (IPD) and are recommended to receive vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23). Antibody concentrations decline following vaccination. We evaluated the immunogenicity and reactogenicity of revaccination and repeat revaccination., Methods: Adults aged 55-74 years were vaccinated with a 1st to 4th dose of PPV23. Participants were eligible for revaccination if a minimum of 6 years had passed since their last dose of PPV23. Blood collected on the day of vaccination and 30 days later was analyzed by ELISA for IgG to five serotypes. Functional antibody activity was measured using an opsonophagocytic killing (OPK) assay. Reactions to vaccination were documented., Results: Subjects were vaccinated with a 1st dose (n=123), 2nd dose (n=121), or 3rd or 4th dose (n=71) of PPV23. The post-vaccination IgG geometric mean concentrations (GMCs) were similar among first-time vaccinees and re-vaccinees for all serotypes with the exception of a lower GMC for serotype 1 in re-vaccinees. The post-vaccination OPK geometric mean titers (GMTs) were similar among first-time vaccinees and re-vaccinees with the exception of a higher GMT for serotype 6B in re-vaccinees. Compared to first-time vaccinees, re-vaccinees reported more joint pain (p=0.004), fatigue (p=0.019), headache (p=0.014), swelling (p=0.006), and moderate limitation in arm movement (p=0.025)., Conclusions: Repeat revaccination with PPV23, administered 6 or more years after the prior dose, was immunogenic and generally well tolerated., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Historically, Alaska experienced cyclic hepatitis A virus (HAV) epidemics, and the HAV rate among Alaska Native people was significantly higher than among other racial/ethnic groups. We evaluated the impact of universal childhood vaccination, initiated in 1996, on HAV epidemiology in Alaska by analyzing HAV cases reported to the State of Alaska. HAV incidence in all age groups declined 98.6% from 60.0/100,000 in 1972-1995 to 0.9/100,000 in 2002-2007. The largest decrease (99.9%) was in Alaska Native people, whose incidence (0.3) in 2002-2007 was lower than the overall U.S. 2007 rate (1.0). Among age groups, the decrease (99.8%) among children aged 0-14 years was the largest. Routine childhood vaccination has nearly eliminated HAV infection in Alaska., ((c) 2010 Elsevier Ltd. All rights reserved.)

Respiratory syncytial virus (RSV) in Alaska Native children from the Yukon Kuskokwim (YK) Delta is associated with a hospitalization rate five times higher than that reported for the general US child population. The role of other viral respiratory pathogens has not been studied in this population. YK Delta children <3 years of age hospitalized with respiratory infections and same aged community control children were prospectively enrolled between October 2005 and September 2007. Polymerase chain reaction detection of viruses was performed on nasopharyngeal samples. Characteristics of hospitalized and asymptomatic control children were analyzed. From October 2005 to September 2007, 440 hospitalized and 425 control children were analyzed. Respiratory viruses were detected in 90% (395) of hospitalized children: 194 (44%) rhinovirus, 131 (30%) adenovirus, 102 (23%) RSV, 77 (18%) para influenza viruses (PIV), 66 (15%) human metapneumovirus (hMPV), 23 (5%) influenza, and 25 (6%) coronavirus. Fifty-two percent (221) of control children had a virus detected, most commonly rhinovirus (33%), and adenovirus (16%). RSV, PIV, hMPV, and influenza were significantly more common in hospitalized cases than control children, but rhinovirus, adenovirus, and coronavirus were not. RSV and hMPV were associated with higher severity of illness. In this study, RSV remains the most important virus associated with respiratory hospitalization, although hMPV and PIV were also common. RSV and hMPV were associated with more severe illness. Rhinovirus and adenovirus were detected in two-thirds of hospitalized children, but their frequent detection in control children made their role in respiratory hospitalization uncertain., ((c) 2010 Wiley-Liss, Inc.)

Objectives: To examine trends in diabetes prevalence, incidence, complications and mortality between 1985 and 2006 among Alaska Native people., Study Design: We used data from the population-based Alaska Native Diabetes Registry, which includes all people who receive care in the Alaska Tribal Health System., Methods: We compared the periods of 1986-1990 and 2002-2006 for diabetes-related amputations, renal replacement and mortality using Poisson regression. Complications and mortality data were examined for trends using Poisson regression. Survival analyses for those diagnosed since 31 December 1985 were performed using the Cox proportional hazard model., Results: Age-adjusted diabetes prevalence increased from 17.3 in 1985 to 47.6/1,000 in 2006. The number of Alaska Native people living in Alaska with diabetes increased from 610 in 1985 to 3,386 in 2006. Diabetes incidence rates have also increased. Comparing age-adjusted rates for the 5-year periods 1986-1990 and 2002-2006, amputations decreased from 5.3 to 2.6/1,000, renal replacement decreased from 3.3 to 1.2/1,000 and mortality decreased from 41.7 to 33.2/1,000. Yearly analyses showed a downward trend for amputations, renal replacement and mortality rates. Survival analyses showed a significantly higher hazard ratio for any amputations, major amputations and renal replacement for the earlier time period compared to the most recent time period., Conclusions: An increase in risk factors, awareness, funding and case-finding may be contributing to the increase in prevalence and incidence of diagnosed diabetes. While diabetes prevalence and incidence are increasing among Alaska Native people, our results suggest that even in remote, rural areas, complications and mortality can be reduced.

Background: Vaccination with conjugate vaccines stimulates T cell-dependent immunity, whereas vaccination with polysaccharide vaccines does not. Thus, vaccination with the 7-valent pneumococcal conjugate vaccine (PCV7) followed by the 23-valent pneumococcal polysaccharide vaccine (PPV23) may offer better protection against invasive pneumococcal disease for older adults than does vaccination with PPV23 alone, which is what is currently recommended., Methods: Alaska Native adults 55-70 years of age with no previous pneumococcal vaccination were randomized to receive (1) PPV23, (2) PCV7 followed 2 months later by PPV23, or (3) PCV7 followed 6 months later by PPV23. Participants recorded reactions after each vaccination. Serum samples collected during the period from May 2002 through February 2003 were tested for serotype-specific immunoglobulin G (IgG) and for opsonophagocytic activity (OPA) against serotypes 1, 4, 6B, 14, and 19F., Results: Vaccination with PCV7 was well tolerated, but persons receiving PCV7 followed by PPV23 reported more local reactions than those receiving only PPV23. All reactions resolved spontaneously within 72 h of receiving vaccine. The geometric mean IgG concentrations of and the median OPA titers to serotypes 4, 6B, 14, and 19F increased in all groups after 1 dose of either PCV7 or PPV23. Serotype-specific geometric mean IgG concentrations and median OPA titers did not differ between any of the groups after vaccination with PPV23, regardless of whether they had previously received PCV7., Conclusions: In this study, PCV7 given 2 or 6 months before PPV23 was well tolerated but did not improve immune response to PPV23 in older Alaska Native adults.

Background & Aims: Persistence of hepatitis B e antigen (HBeAg) in chronic hepatitis B has been associated with increased risk for development of cirrhosis and hepatocellular carcinoma. Five hepatitis B virus genotypes were identified in Alaska Native persons; we analyzed clearance of HBeAg by age and genotype., Methods: In this prospective cohort study, 1158 Alaska Native persons throughout Alaska were tested serially for HBeAg for a median of 20.5 years and were genotyped. Initial and final HBeAg-positive specimens, time to clearance, age at clearance, and subsequent HBeAg results were analyzed for persons initially HBeAg-positive. Subsequent HBeAg results were analyzed for persons initially negative., Results: Genotypes A, B, C, D, and F were identified. Genotype C persons initially HBeAg-positive were more likely than those with other genotypes to be positive on initial and final specimens (P < .001 for each) and time to HBeAg clearance was longer (P < .001). Age at which 50% of persons cleared HBeAg was <20 years for those infected with genotypes A, B, D, and F and 47.8 years in genotype C (P < .001). After losing HBeAg, those with genotypes C and F were more likely to revert to the HBeAg-positive state (P < .001)., Conclusions: Genotype may have a strong effect on mode of transmission and outcome. Genotype C may have been responsible for most perinatal transmission, given that seroconversion from HBeAg occurs decades later than in other genotypes.

From 1993 to 1996, Alaska Native infants younger than 1 year of age from the Yukon-Kuskokwim Delta region in Alaska experienced a respiratory syncytial virus (RSV) hospitalization rate 5 times higher than the U.S. general infant population rate. This article describes the trends in hospitalization and prolonged annual season of RSV hospitalizations in Yukon-Kuskokwim children from 1993 to 2004 and discusses factors associated with high rates of RSV hospitalization and the impact of interventions to decrease RSV hospitalizations in this population.

Background: The highest incidence of hepatitis B virus (HBV)-associated vasculitis in the world has been reported in Alaska Natives. We examined the incidence of HBV-associated vasculitis before and after mass HBV vaccine immunization and the association between HBV genotype and vasculitis in a population-based cohort study in Alaska natives chronically infected with HBV., Methods: Genotyping was performed in vasculitis cases and 644 hepatitis B-positive controls without vasculitis using polymerase chain reaction and sequencing of the S gene. Occurrence of HBV vasculitis from 1974 to 2004 was calculated. HBV vasculitis patients and controls were also tested for basal core promoter and precore mutations., Results: Fifteen cases of HBV-associated vasculitis were identified: 13 (86%) had genotype D and one each genotype A and F. Genotype D was more commonly found in patients with vasculitis than controls [odd ratio (OR)=5.9, confidence interval (95% CI) 1.2, 21.8; P<0.015)., Conclusions: HBV-associated vasculitis was associated with genotype D.

Context: With routine childhood vaccination using heptavalent pneumococcal conjugate vaccine, one concern has been the potential for emergence and expansion of replacement disease caused by serotypes not contained in the heptavalent conjugate vaccine., Objective: To determine whether replacement disease is associated with the overall decline in invasive pneumococcal disease among Alaska Native children., Design, Setting, and Patients: Alaska statewide longitudinal population-based laboratory surveillance of invasive Streptococcus pneumoniae infections from January 1, 1995, through December 31, 2006., Main Outcome Measures: Incidence and types of pneumococcal disease in children younger than 2 years., Results: In the first 3 years after introduction of routine vaccination with heptavalent pneumococcal conjugate vaccine, overall invasive pneumococcal disease decreased 67% in Alaska Native children younger than 2 years (from 403.2 per 100,000 in 1995-2000 to 134.3 per 100,000 per year in 2001-2003, P<.001). However, between 2001-2003 and 2004-2006, there was an 82% increase in invasive disease in Alaska Native children younger than 2 years to 244.6/100,000 (P = .02). Since 2004, the invasive pneumococcal disease rate caused by nonvaccine serotypes has increased 140% compared with the prevaccine period (from 95.1 per 100,000 in 1995-2000 to 228.6 in 2004-2006, P = .001). During the same period, there was a 96% decrease in heptavalent vaccine serotype disease. Serotype 19A accounted for 28.3% of invasive pneumococcal disease among Alaska children younger than 2 years during 2004-2006. There was no significant increase in nonvaccine disease in non-Native Alaska children younger than 2 years., Conclusions: Alaska Native children are experiencing replacement invasive pneumococcal disease with serotypes not covered by heptavalent pneumococcal conjugate vaccine. The demonstration of replacement invasive pneumococcal disease emphasizes the importance of ongoing surveillance and development of expanded valency vaccines.

Alaska Native persons have age-adjusted invasive pneumococcal disease (IPD) rates two- to three-fold greater than non-Native Alaskans. To characterize IPD epidemiology and 23-valent polysaccharide pneumococcal vaccine (PPV-23) effectiveness in Alaska Native adults we reviewed IPD cases from Alaska-wide, laboratory-based surveillance. Sterile site isolates were serotyped. Vaccine effectiveness (VE) was estimated using the indirect cohort method. 394 cases (44.5 cases/100,000/year) occurred in 374 Alaska Native adults (36.0% aged > or =55 years). Underlying conditions included heavy alcohol use (65.7%), smoking (60.8%) and COPD (25.0%). Overall VE was 75% (95% confidence interval [CI]: 27%, 91%) but declined with increasing age; for persons > or =55 years (VE=<0; 95% CI: <0, 78%; p=0.713). Alaska Native adults experience high rates of IPD. The majority of IPD cases occurred in persons with underlying conditions and behaviors associated with increased risk of IPD in other populations. PPV-23 vaccine effectiveness was confirmed in younger Alaska Native adults but not among adults > or =55 years.

Background: The development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection has been associated with specific HBV genotypes and the presence of specific mutations., Methods: From a cohort of Alaska Native people with chronic HBV infection, we genotyped 47 patients with HCC and 1129 patients without HCC, and we tested patients with HCC and control patients for mutations in the basal core promoter and precore regions., Results: Genotype F was found in 68% of patients with HCC, versus 18% of those without HCC (P<.001). For patients with genotype F, the median age at diagnosis of HCC was lower than that for patients with other genotypes (22.5 vs. 60 years, respectively; P=.002). Overall, there were no significant differences in the number of basal core promoter and precore region mutations between patients with HCC and control patients., Conclusions: We found a significant association between genotype F and the development of HCC among Alaska Native people with chronic HBV infection but no significant association between HCC and basal core promoter or precore mutations in genotype F.

Background: During 1993 to 1996, Alaska Native infants <1 year of age from the Yukon Kuskokwim (YK) Delta in Alaska experienced a respiratory syncytial virus (RSV) hospitalization rate 5 times the U.S. general infant population rate. We describe trends in lower respiratory tract infection (LRTI) and RSV hospitalizations in YK children from 1994 to 2004., Methods: We abstracted hospital dates, RSV test results and clinical information from the hospital records for YK children <3 years of age hospitalized between July 1994 and June 2004., Results: : The RSV hospitalization rate in YK Delta children <1 year of age decreased from 178 per 1000 infants per year (1994-1997) to 104 per 1000 infants per year (2001-2004) (P < 0.001), and the RSV hospitalization rate for premature infants decreased from 317 to 123 per 1000 infants per year (P < 0.001). The risk reduction for RSV hospitalization was greater in premature (relative risk, 0.39) than in term infants (relative risk, 0.60; P = 0.04). The rate of non-RSV LRTI hospitalizations increased from 153 to 215 per 1000 infants per year (P < 0.001). The median RSV season length was 30.5 weeks. Pneumonia was diagnosed in more than half of RSV admissions., Conclusions: In YK infants, the RSV hospitalization rate decreased by one-third between 1994 and 2004; however, the overall LRTI hospitalization rate did not change. The median RSV season was twice as long as for the U.S. population. Palivizumab prophylaxis may be responsible for the larger decrease in the RSV hospitalization rate among premature infants; however, the 2001-2004 RSV hospitalization rate among YK infants remained 3 times higher than the U.S. infant rate.

Background: The relationship between atopic disease and serum IgE levels varies among populations and geographic regions. The close association of atopy with IgE may not occur in subarctic populations as it does in developed countries in temperate climates., Objective: To evaluate the relationship between total and specific IgE concentrations and clinical atopy in 5- to 8-year-old Alaskan native children., Methods: Medical record reviews, interviews, physical examinations, serum IgE measurements, and radioallergosorbent testing (RAST) were performed., Results: The IgE geometric mean was 122.1 IU/mL. Fifty-eight percent of patients had IgE levels greater than 70 IU/mL, and 17% had levels greater than 1,000 IU/mL; 14% had RAST values greater than 0.35 kU/L. Both IgE levels greater than 70 IU/mL and greater than 1,000 IU/mL were associated with RAST values greater than 0.35 IU/L (P = .004) and early wheezing (P = .005) but not with current wheezing, asthma, eczema, or a history of allergies. A RAST value greater than 3.51 kU/L was associated with eczema (P = .04) but not with allergies or wheezing. Children with current wheezing were more likely to have allergies (P = .03) but not eczema, an IgE level greater than 70 IU/mL, or a positive RAST value. Children hospitalized with respiratory syncytial virus (RSV) were not more likely than controls to have current wheezing., Conclusions: Elevated serum IgE concentrations, including levels greater than 1,000 IU/mL, are common among Alaskan native children; positive RAST reactions to aeroallergens are not. The IgE levels do not relate to wheezing, eczema, a history of allergies, or past hospitalization for RSV infection but likely reflect infections other than RSV and environmental factors in subarctic indigenous populations.

Background: Despite routine vaccination and declining disease rates, Haemophilus influenzae type b (Hib) invasive disease still occurs in rural Alaska. Colonization studies indicate persistent transmission of Hib among village residents, including adults. As part of a project to eliminate Hib carriage in three rural villages, we evaluated a cohort of Alaska adults for antibody response and reactogenicity to a single dose of Hib conjugate vaccine (HbOC)., Methods: 75 previously unvaccinated, randomly-selected adults in one village received a single dose of HbOC vaccine and completed a side-effects diary. Sera and oropharyngeal specimens were collected at baseline, two months and one year., Results: No participants were colonized with Hib or reported serious side-effects. At baseline, 97% of adults had IgG anti-PRP concentrations > or = 0.15 microg/mL, 69% > or = 1 microg/mL, and 28% > or = 5 microg/mL. Two months post-vaccination, 100% of participants had concentrations > or = 0.15 microg/mL, 93% > or = 1 microg/mL, and 86% > or = 5 microg/mL. After 1 year, 98% had IgG anti-PRP concentrations > or = 0.15 microg/mL, 86% > or = 1 microg/mL, and 67% > or = 5 microg/mL. GMCs were 1.9, 33.3 and 8.4 microg/mL at baseline, 2 months and 1 year post-vaccine, respectively (p < 0.01). Serum bactericidal activity increased from a baseline geometric mean titer of 2,205 to 8,349 two months post vaccination and declined to 1102 after one year., Conclusions: HbOC vaccine was immunogenic and well-tolerated among Alaskan adults. Nearly 90% of the adults developed an antibody level associated with protection against Hib colonization which persisted for 1 year in 67% of participants.

We evaluated invasive pneumococcal disease (IPD), antimicrobial resistance and nasopharyngeal colonization before and after introduction of pneumococcal conjugate vaccine (PCV7) in Alaska Natives (AN), a population with high IPD rates. We obtained IPD rates from population-based surveillance. Colonization was determined from annual surveys among rural AN of all ages and from urban children. After vaccine introduction, vaccine-type IPD rates declined by 91% among AN children <2 years, by 80% among non-Natives <2 years, and by 40% for adults of all races (P<0.001 each). IPD decreased for isolates resistant to penicillin, erythromycin and cotrimoxazole (P<0.001 each). Vaccine-type colonization decreased among rural and urban children <5 years and among rural adults (P<0.001 each). PCV7 vaccine has eliminated a longstanding disparity of vaccine-type IPD for AN children. Decreased vaccine-type colonization and IPD in adults demonstrate indirect vaccine effects.

Background: Alaska Native (AN) children were at high risk of acquiring hepatitis B virus (HBV) infection before vaccination began in 1983. We evaluated the long-term protection from hepatitis B (HB) vaccination among AN children immunized when infants., Methods: During 1984-1995, we recruited a convenience sample of AN children who had received a three dose series of HB vaccine starting at birth and had serum antibody to hepatitis B (anti-HBs) concentrations of >/= 10 mIU/mL at 7-26 months of age. We evaluated anti-HBs concentrations and the presence of anti-HBc in participants' sera every other year up to age 16 years. Anti-HB core antigen (anti-HBc)-positive specimens were tested for hepatitis B surface antigen and for HBV DNA., Results: We followed 334 children for 3151 person-years (median, 10 years per child) with 1610 specimens collected. Anti-HBs concentrations dropped rapidly among all participants. Among children 2, 5 and 10 years of age, 37 of 79 (47%), 33 of 176 (19%) and 8 of 95 (8%), respectively, had anti-HBs concentrations of >/= 10 mIU/mL. Receipt of recombinant vaccine was significantly associated with a more rapid antibody decline (P < 0.001). Six (1.8%) children acquired anti-HBc, 3 of whom had definite breakthrough infections (at least 2 consecutive anti-HBc-positive specimens or at least 1 anti-HBc-positive specimen and HBV DNA detection by PCR). None of these children had detectable hepatitis B surface antigen, and none had symptoms of hepatitis., Conclusions: Anti-HBs concentrations declined over time among AN infants successfully immunized with HB vaccine starting at birth. Transient anti-HBc appeared in a small percentage of children; however, none developed clinical signs of hepatitis or chronic HBV infection.

Background: Following vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV), pneumococcal antibody levels decline to prevaccination levels within 6-10 years. The Advisory Committee on Immunization Practices does not recommend routine revaccination because data on the safety and effectiveness of additional doses are insufficient., Methods: To determine whether medically attended adverse events occur more frequently after the third dose of PPV than after the first or second dose, we performed a retrospective review of medical records from a computer database for health care facilities that serve more than one-half of the Alaska Native population. All persons who had received > or = 3 PPV doses (n = 179) were included in the review, as were a randomly selected comparison group of 181 persons who had received 1 or 2 doses., Results: Only 1 (0.55%) of 179 persons who had received > or = 3 PPV doses and 4 (2.76%) of 181 persons in the comparison group had a medically attended adverse event, and no severe adverse events were recorded., Conclusion: We found no difference in the risk of medically attended adverse events following > or = 3 doses of PPV, compared with 1 or 2 doses.

Background: The duration of protection afforded by hepatitis B vaccination is unknown., Objective: To determine antibody persistence and protection from hepatitis B virus (HBV) infection., Design: Prospective cohort study., Setting: 15 villages in southwest Alaska., Participants: 1578 Alaska Natives vaccinated at age 6 months or older., Intervention: During 1981-1982, participants received 3 doses of plasma-derived hepatitis B vaccine. This cohort was followed annually over the first 11 years, and 841 (53%) persons were tested at 15 years., Measurements: Antibody to hepatitis B surface antigen (anti-HBs), markers of HBV infection, and testing to identify HBV variants., Results: Levels of anti-HBs in the cohort decreased from a geometric mean concentration of 822 mIU/mL after vaccination to 27 mIU/mL at 15 years. Initial anti-HBs level, older age at vaccination, and male sex were associated with persistence of higher anti-HBs levels at 15 years when analyzed by a longitudinal linear mixed model. After adjustment for initial anti-HBs level and sex, those vaccinated at age 6 months to 4 years had the lowest anti-HBs level at 15 years. Asymptomatic breakthrough infections were detected in 16 participants and occurred more frequently in persons who did not respond to vaccination than those who responded (P = 0.01). Among infected persons with viremia, 2 were infected with wild-type HBV and 4 had HBV surface glycoprotein variants, generally accompanied by wild-type HBV., Limitations: The loss of participants to follow-up at 15 years was 47%. However, characteristics of persons tested were similar to those of persons lost to follow-up., Conclusions: Hepatitis B vaccination strongly protected against infection for at least 15 years in all age groups. Antibody levels decreased the most among persons immunized at 4 years of age or younger.

Objective: To compare characteristics of persons in rural northern communities who participated in a study on antimicrobial use and drug-resistant Streptococcus pneumoniae (SP) to those who did not participate., Study Design: The original study (1998--2000) was a community-based, controlled intervention trial designed to determine the penicillin susceptibility of nasopharyngeal SP isolates in relation to community-wide use of antibiotics. The study continued after 2000, in a subset of the original communities, to prospectively evaluate the impact of the heptavalent pneumococcal conjugate vaccine on the carriage of SP. The results presented here are an analysis of the first five years of data., Methods: We conducted annual surveys (1998--2002) for nasopharyngeal colonization of SP using a volunteer sample of residents in rural communities. Medical chart reviews for health clinic visitation and antibiotic use were completed for all village residents., Results: Participants were younger (22.8 vs. 28.4 years), had more health clinic utilization (3.3 vs. 2.4 visits) and received more antibiotics (1.0 vs. 0.6 courses) than non-participants. Differences between participants and non-participants were similar across all years of the study., Conclusions: Our study provides further empirical evidence that selection bias should be considered when designing studies. However, a volunteer sample provided internal consistency for comparison of our main study outcomes across time.

Objectives: Studies on the natural history and outcome of chronic hepatitis C virus (HCV) infection differ regarding the proportion of persons who develop serious sequelae over time. Most of these studies use an estimated date of HCV infection based on risk factor data obtained from patient interviews. The date of HCV infection is often estimated using the year of a pre-1992 blood transfusion (BT), or the first year of injecting drug use (IDU). We sought to determine the accuracy of these dates obtained by interview., Methods: We compared BT dates reported by patients in a long-term HCV outcome study to dates confirmed in a BT-Lookback project, and also compared the reported first year of IDU to seroconversion dates estimated from HCV tests on historical sera., Results: Of 28 BT recipients who were interviewed in the HCV outcome study and identified in the Lookback project, 14 (50%; 95% CI: 31-69%) were unaware they had received a BT. Of 25 persons identified in the BT-Lookback project with historical sera available, 9 (36%; 95% CI: 19-57%) had anti-HCV results that did not correlate with their confirmed BT date. Of 216 persons with a history of IDU and historical serum samples available, 66 (31%; 95% CI: 25-37%) had anti-HCV results that did not correlate with their reported first year of IDU., Conclusions: Inaccuracies in the length of HCV could occur in outcome studies that rely on patient recall of risk-factor history. Statistical methods that incorporate the uncertainty in assigning infection date are needed., (Copyright 2004 American College of Gastroenterology)

Background: The duration of protection after hepatitis B vaccination of infants is unknown., Methods: We determined antibody to hepatitis B surface antigen (anti-HBs) at 4-13 years of age in 363 low risk children who had been vaccinated starting at birth with hepatitis B vaccine. Those with nonprotective titers (<10 mIU/mL) received a booster dose. We similarly followed 16 children of hepatitis B surface antigen (HBsAg)-positive mothers., Results: Of low risk infants receiving a plasma-derived vaccine, 41% (42 of 102) of those whose primary response was unknown and 24% (4 of 17) who had initially responded retained protective titers (> or = 10 mIU/mL) of anti-HBs at 9 and 13 years, respectively. Of those who did not have protective antibody titers, 61% (33 of 54) and 67% (8 of 12), respectively, responded to a booster dose. In children of HBsAg-positive mothers, 31% retained protective anti-HBs at 12 years, and 90% (9 of 10) with nonprotective titers responded to a booster. In low risk children initially receiving a recombinant vaccine, 12.5% (26 of 208) and none (0 of 36) retained protective anti-HBs titers at 5 and 7 years of age, respectively. Of those who did not have protective titers, 90% (120 of 134) and 91% (32 of 35), respectively, responded to a booster., Conclusions: Anti-HBs disappeared by 5 years of age in most children who were vaccinated with hepatitis B vaccine from birth. Although most children showed immunologic memory, one-third failed to demonstrate an anamnestic response to a booster dose. Additional long term studies of low risk infants are needed to determine duration of protection and the necessity for or timing of booster doses.

Current immunization schedules for hepatitis A vaccine specify administration of a booster within 6-12 or 6-18 months of the primary dose. However, there may be circumstances that disrupt this schedule and the efficacy of administering a booster beyond the recommended time is a practical concern for healthcare providers. In this study, a booster was administered to 268 participants (137: <18 years old), an average of 27 months (range 20-31) after the primary dose. In those tested after the booster, the median anti-HAV GMT was 1544 milli-international units per milliliter (mIU/ml). Response to a delayed booster was strong in children over 2 years old (GMT 1500-1960 mIU/ml) and adults (GMT 1622 mIU/ml), but was significantly lower in children under 2 years old (GMT 1109 mIU/ml). Findings suggest a booster administered 20-31 months after the primary dose is immunogenic and GMT in persons >2 years of age were comparable to those seen in adults and children who receive hepatitis A vaccine per schedule.

Objective: The incidence of hospitalization for respiratory syncytial virus (RSV) infection among Alaska Native children is much higher than among non-Native populations in the United States. We conducted this study to better understand factors associated with hospitalization attributable to RSV infection in this high-risk population., Design: Case-control study, including collection of cord blood for RSV-neutralizing antibody measurement., Setting: Remote region of southwest Alaska served by 1 regional hospital and 2 referral hospitals., Subjects: Case-patients identified through surveillance for RSV infection and matched control subjects without acute respiratory infection hospitalization., Results: Breastfeeding was associated with a lower risk of RSV hospitalization (odds ratio: 0.34), whereas underlying medical conditions (primarily prematurity) were associated with increased risk (odds ratio: 6.25). Environmental factors associated with a higher risk of hospitalization included household crowding (4 or more children in the household and crowding index > or =2). The level of maternal RSV-neutralizing antibody was not associated with the risk of hospitalization., Conclusions: In this region with extremely high risk of RSV hospitalization, several measures, such as encouraging breastfeeding and reducing household crowding, could reduce the risk of hospitalization attributable to RSV.