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The International Circumpolar Surveillance (ICS) program is a population-based surveillance network for invasive bacterial diseases throughout Arctic countries and territories. The ICS quality control program for Streptococcus pneumoniae serotyping and antimicrobial susceptibility testing has been ongoing since 1999. Current participating laboratories include the Provincial Laboratory for Public Health in Edmonton, Alberta; Laboratoire de santé publique du Québec in Sainte-Anne-de-Bellevue, Québec; the Centers for Disease Control's Arctic Investigations Program in Anchorage, Alaska; the Neisseria and Streptococcus Reference Laboratory at Statens Serum Institut in Copenhagen, Denmark; the Department of Clinical Microbiology, Landspitali in Reykjavik, Iceland; and Public Health Agency of Canada's National Microbiology Laboratory in Winnipeg, Manitoba. From 2009 to 2020, 140 isolates of S. pneumoniae were distributed among the six laboratories as part of the quality control program. Overall serotype concordance was 96.9%, with 99.3% concordance to pool level. All participating laboratories had individual concordance rates >92% for serotype and >97% for pool. Overall concordance by modal minimum inhibitory concentration (MIC) for testing done by broth microdilution or Etest was 99.1%, and >98% for all antimicrobials tested. Categorical concordance was >98% by both CLSI and EUCAST criteria. For two laboratories performing disc diffusion, rates of concordance by modal MIC were >97% for most antimicrobials, except chloramphenicol (>93%) and trimethoprim/sulfamethoxazole (>88%). Data collected from 12 years of the ICS quality control program for S. pneumoniae demonstrate excellent (≥95%) overall concordance for serotype and antimicrobial susceptibility testing results across six laboratories., Importance: Arctic populations experience several social and physical challenges that lead to the increased spread and incidence of invasive diseases. The International Circumpolar Surveillance (ICS) program was developed to monitor five invasive bacterial diseases in Arctic countries and territories. Each ICS organism has a corresponding interlaboratory quality control (QC) program for laboratory-based typing, to ensure the technical precision and accuracy of reference testing services for these regions, and identify and correct potential problems. Here, we describe the results of the ICS Streptococcus pneumoniae QC program, from 2009 to 2020. Excellent overall concordance was achieved for serotype and antimicrobial susceptibility testing results across six laboratories. Ongoing participation in these QC programs ensures the continuation of quality surveillance systems within Arctic populations that experience health disparities., Competing Interests: H.-C. Slotved is presently involved in Pfizer-supported pneumococcal projects and has also participated in consultations with MSD. G.J. Tyrrell has received funding from Merck for pneumococcal research. K.G. Kristinsson has received support for investigator-initiated studies from GlaxoSmithKline Biologicals SA. All other authors have no conflicts to declare.

Background and Aims: A functional cure and therapeutic end point of chronic HBV infection is defined as the clearance of HBsAg from serum. Little is known about the long-term durability of HBsAg loss in the Alaskan Native population., Approach and Results: We performed a retrospective cohort study of Alaska Native patients with chronic HBV-monoinfection from January 1982 through December 2019. The original group in this cohort was identified during a 1982 to 1987 population-based screening for 3 HBV serologic markers in 53,000 Alaska Native persons. With close to 32,000 years of follow-up, we assessed the frequency and duration of HBsAg seroclearance (HBsAg-negative for > 6 mo). We examined factors associated with HBsAg clearance and followed persons for a median of 13.1 years afterward to assess the durability of HBsAg clearance. Among 1079 persons with an average length of follow-up of 33 years, 260 (24%) cleared HBsAg at a constant rate of 0.82% per person/per year. Of the 260 persons who cleared, 249 (96%) remained HBsAg-negative, while 11 persons had ≥ 2 transient HBsAg-positive results in subsequent follow-up., Conclusions: Of the patients with chronic HBV monoinfection, 0.82% of people per year achieved a functional cure. HBsAg seroclearance was durable for treated and nontreated patients and lasted, on average, over 13 years without seroreversion.

Background: Haemophilus influenzae (Hi) can cause severe disease in children. This study aimed to identify risk factors related to invasive Hi disease in Alaska children and evaluate carriage in people around them., Methods: From 2005 to 2011, we investigated episodes of invasive, typeable Hi disease in Alaska children <10 years old. Three age-matched control children were enrolled for each case-patient. We evaluated oropharyngeal Hi carriage in people in close contact with Hi case-patients (contacts) as well as control children and their household members. Individual and household risk factors for illness and carriage were evaluated using questionnaires and chart reviews., Results: Thirty-eight of 44 (86%) children with invasive, typeable Hi disease were recruited: 20 Hi serotype a (53%), 13 serotype b (Hib) (34%) and 5 serotype f (13%). Children with the invasive Hi disease were more likely than controls to have underlying health problems (67% vs. 24%, P = 0.001), other carriers of any Hi in their household (61% vs. 15%, P < 0.001), and inadequate Hib vaccination (26% vs. 9%, P = 0.005). People who carried Hi were younger than noncarriers (mean 12.7 vs. 18.0 years, P = 0.008). The carriage was clustered within case-patient households, with carriage in 19% of household contacts, while only 6.3% of nonhousehold contacts and 5.5% of noncontacts carried the Hi serotype of interest ( P < 0.001)., Conclusions: Factors associated with invasive Hi disease in children included underlying health problems, household carriage and inadequate Hib vaccination. The high level of carriage in case-patient households is important to consider when evaluating treatment and prophylaxis strategies., Competing Interests: The authors have no conflicts of interest to disclose.

Background: Persistent human papillomavirus (HPV) infection can cause anogenital and oropharyngeal cancers. Many HPV infections and HPV-associated cancers are vaccine-preventable. Studies suggest long-term persistence of vaccine-induced antibodies. However, data are limited among Alaska Native people., Methods: During 2011-2014, we enrolled Alaska Native children aged 9-14 years who received a 3-dose series of quadrivalent HPV vaccine (4vHPV). We collected sera at 1 month and 1, 2, 3, and 5 years post-vaccination to evaluate trends in type-specific immunoglobulin G antibody concentrations for the 4vHPV types (HPV 6/11/16/18)., Results: All participants (N = 469) had detectable antibodies against all 4vHPV types at all timepoints post-vaccination. For all 4vHPV types, antibody levels peaked by 1 month post-vaccination and gradually declined in subsequent years. At 5 years post-vaccination, antibody levels were higher among children who received 4vHPV at a younger age., Conclusions: Alaska Native children maintained antibodies against all 4vHPV types at 5 years post-vaccination., 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.)

Background: Adults aged ≥65 years, adults with certain underlying medical conditions, and persons experiencing homelessness are at increased risk for invasive pneumococcal disease (IPD). Two new pneumococcal conjugate vaccines, 15-valent pneumococcal conjugate vaccine (PCV15) and 20-valent pneumococcal conjugate vaccine (PCV20), were recently approved for use in US adults. We describe the epidemiology of IPD among Alaska adults and estimate the proportion of IPD cases potentially preventable by new vaccines., Methods: We used statewide, laboratory-based surveillance data to calculate and compare IPD incidence rates and 95% confidence intervals (CIs) among Alaska adults aged ≥18 years during 2011-2020 and estimate the proportion of IPD cases that were caused by serotypes in PCV15 and PCV20., Results: During 2011-2020, 1164 IPD cases were reported among Alaska adults for an average annual incidence of 21.3 cases per 100 000 adults per year (95% CI, 20.1-22.5). Incidence increased significantly during the study period (P < .01). IPD incidence among Alaska Native adults was 4.7 times higher than among non-Alaska Native adults (95% CI, 4.2-5.2). Among adults experiencing homelessness in Anchorage, IPD incidence was 72 times higher than in the general adult population (95% CI, 59-89). Overall, 1032 (89%) Alaska adults with IPD had an indication for pneumococcal vaccine according to updated vaccination guidelines; 456 (39%) and 700 (60%) cases were caused by serotypes in PCV15 and PCV20, respectively., Conclusions: Use of PCV15 and PCV20 could substantially reduce IPD among adults in Alaska, including Alaska Native adults and adults experiencing homelessness., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

The population in rural southwest Alaska has been disproportionately affected by COVID-19. To assess the benefit of COVID-19 vaccines, we analyzed data from the regional health system. We estimated vaccine effectiveness (VE) during January 16-December 3, 2021, against symptomatic SARS-CoV-2 infection after a primary series or booster dose, and overall VE against hospitalization. VE of a primary series against symptomatic infection among adult residents was 91.3% (95% CI: 85.7, 95.2) during January 16-May 7, 2021, 50.3% (95% CI, 41.1%-58.8%) during July 17-September 24, and 37.0% (95% CI, 27.8-45.0) during September 25-December 3, 2021; VE of a booster dose during September 25-December 3, 2021, was 92.1% (95% CI: 87.2-95.2). During the overall study period, VE against hospitalization was 91.9% (95% CI: 85.4-95.5). COVID-19 vaccination offered strong protection against hospitalization and a booster dose restored protection against symptomatic infection., 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.)

Invasive Haemophilus influenzae type a (iHia) disease was detected in Alaska and Northern Canada in 2002 and 2000, respectively. From 2006 to 2017, 164 iHia cases (Alaska=53, Northern Canada=111) were reported. Rates of iHia disease per 100,000 persons were higher in Northern Canada compared to Alaska and were significantly higher in Indigenous (Alaska 2.8, Northern Canada 9.5) compared to non-Indigenous populations (Alaska 0.1, Northern Canada=0.4). Disease rates were highest in Indigenous children <2 years of age (Alaska 56.2, Northern Canada=144.1) and significantly higher than in non-Indigenous children <2 (Alaska 0.1, Northern Canada 0.4). The most common clinical presentation in children <5 years was meningitis of age and pneumonia in persons ≥5 years old. Most patients were hospitalised (Alaska=87%, Northern Canada=89%) and fatality was similar (Alaska=11%, Northern Canada=10%). MLST testing showed sequence types ST23 and ST576 in Northern Canada and ST576, ST23 and ST56 in Alaska. Alaska and Northern Canada have high rates of iHia disease. A vaccine is needed in these regions to protect young children.

Background: Hepatitis C virus (HCV) infection incidence rates in the United States have increased since 2010 as a byproduct of the opioid crisis despite the introduction of direct-acting antiviral agents in 2013. HCV infection is associated with higher rates of liver-related and nonhepatic causes of death., Methods: This study compared demographic characteristics and age-adjusted death rates from 1995 to 2016 among Alaska Native (AN) adults infected with HCV (AK-HepC) to rates among the AN and non-AN adult populations living in Alaska. Liver-related disease (LRD) and other disease-specific age-adjusted death rates were compared between the populations., Results: The all-cause death rate among the AK-HepC cohort was 2.2- and 3.4-fold higher than AN and non-AN adults, respectively, and remained stable over time in all populations. The LRD death rate among the AK-HepC cohort was 18- and 11-fold higher than the non-AN and AN, respectively. The liver cancer rate among the AK-HepC cohort was 26-fold higher compared to the Alaska statewide population. The AK-HepC cohort had elevated rates of death associated with nonhepatic diseases with circulatory disease having the highest rate in all populations. Among liver cancer deaths in the AK-HepC cohort, 32% had HCV listed as a contributing cause of death on the death certificate., Conclusions: Death rates in the AK-HepC cohort remained stable since 1995 and higher compared to the general population. People with HCV infection had an elevated risk for all-cause, liver-related, and nonhepatic causes of death. Hepatitis C infection may be underrepresented as a cause of mortality in the United States., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Sara S. Bressler et al.)

Objectives: This study describes the changes in lower respiratory tract infection (LRTI) rates from 1998 to 2014 among hospitalized American Indian/Alaska Native (AI/AN) adults residing in Alaska and other Indian Health Service (IHS) regions., Methods: Age-adjusted hospital discharge rates and rate ratios were calculated from the IHS Direct and Contract Health Services Inpatient Dataset, IHS National Patient Information Reporting System for AI/AN adults ≥18 years, hospitalized at an IHS-operated, tribally operated, or contract hospital with an LRTI-associated diagnosis during 1998-2014., Results: Overall, there were 13 733 LRTI-associated hospitalizations in Alaska (1998-2014), with an age-adjusted rate of 13.7/1000 adults. Among non-Alaska (non-AK) AI/AN, there were a total of 79 170 hospitalizations, with a rate of 8.6/1000 adults. In the pre-PCV7 and pre-PCV13 periods, LRTI rates were higher in Alaska (AK) AI/AN (12.4 and 14.1, respectively) when compared to non-AK AI/AN (10.1 and 9.1, respectively) (P < 0.0001). In the post-PCV7 and post-PCV13 periods, LRTI rates were also higher in AK (13.5 and 15.0, respectively) compared to non-AK (9.2 and 7.3, respectively) (P < 0.0001)., Conclusions: Over the study period, a 26% increase in rates of LRTI among adult AI/AN residing in AK compared with a 38% decrease in rates among AI/AN residing in non-AK were observed. This disparity is likely due to a variety of factors such as tobacco use, crowding, etc. Strategies to reduce LRTI in AI/AN adults are needed., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Haemophilus influenzae serotype a (Hia) can cause invasive disease similar to serotype b; no Hia vaccine is available. We describe the epidemiology of invasive Hia disease in the United States overall and specifically in Alaska during 2008-2017., Methods: Active population- and laboratory-based surveillance for invasive Hia disease was conducted through Active Bacterial Core surveillance sites and from Alaska statewide invasive bacterial disease surveillance. Sterile-site isolates were serotyped via slide agglutination or real-time polymerase chain reaction. Incidences in cases per 100 000 were calculated., Results: From 2008 to 2017, an estimated average of 306 invasive Hia disease cases occurred annually in the United States (estimated annual incidence: 0.10); incidence increased by an average of 11.1% annually. Overall, 42.7% of cases were in children aged <5 years (incidence: 0.64), with highest incidence among children aged <1 year (1.60). Case fatality was 7.8% overall and was highest among adults aged ≥65 years (15.1%). Among children aged <5 years, the incidence was 17 times higher among American Indian and Alaska Native (AI/AN) children (8.29) than among children of all other races combined (0.49). In Alaska, incidences among all ages (0.68) and among children aged <1 year (24.73) were nearly 6 and 14 times higher, respectively, than corresponding US incidences. Case fatality in Alaska was 10.2%, and the vast majority (93.9%) of cases occurred among AI/AN., Conclusions: Incidence of invasive Hia disease has increased since 2008, with the highest burden among AI/AN children. These data can inform prevention strategies, including Hia vaccine development., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: Between May and July 2018, 4 Haemophilus influenzae serotype a (Hia) infections occurred in a remote Alaska community. We performed a public health response to prevent further illness and understand Hia carriage., Methods: We collected oropharyngeal samples community-wide to evaluate baseline carriage. Risk factors were evaluated by interview. We offered prophylactic rifampin to individuals in contact with invasive Hia patients (contacts) and to all children aged <10 years. Oropharyngeal samples were collected again 8 weeks after rifampin distribution. Samples were tested using real-time polymerase chain reaction and culture., Results: At baseline, 4 of 27 (14.8%) contacts and 7 of 364 (1.9%) noncontacts (P < .01) carried Hia. Contacts aged <10 years were more likely to carry Hia at any timepoint (11/18 [61%]) compared to contacts aged ≥10 years (3/34 [8.8%]), noncontacts aged <10 years (2/139 [1.4%]), and noncontacts ≥10 years (6/276 [2.2%]) (P < .001 for all). Hia carriers were clustered in 9 households (7% of total households). At the household level, carriage was associated with households with ≥1 contact (prevalence ratio [PR], 5.6 [95% confidence interval {CI}, 1.3-21.6]), crowding (PR, 7.7 [95% CI, 1.1-199.5]), and ≥3 tobacco users (PR, 5.0 [95% CI, 1.2-19.6]). Elevated carriage prevalence persisted in contacts compared to noncontacts 8 weeks after rifampin distribution (6/25 [24%] contacts, 2/114 [1.8%] noncontacts; P < .001)., Conclusions: Hia carriage prevalence was significantly higher among contacts than noncontacts. Rifampin prophylaxis did not result in a reduction of Hia carriage prevalence in this community., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Following increases in reported cases of hepatitis A, we assessed the impact of hepatitis A vaccine in Alaska Native persons. During 1996-2018, only 6 cases of hepatitis A were identified, all in unvaccinated adults. Populations can be protected against hepatitis A by achieving sufficient vaccination coverage over time., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: Stomach cancer incidence and mortality rates are declining across circumpolar nations, but the burden may not be distributed equally across subpopulations, including Indigenous peoples. Our objective was to examine stomach cancer incidence and mortality trends across circumpolar populations., Methods: Cancer incidence and mortality data from 1999-2016 were obtained from the Canadian Cancer Registry, Canadian Vital Statistics, CDC WONDER, NORDCAN, Northwestern Russian cancer registries, and National Cancer Reports. The direct method was used to calculate 10-year rolling age-standardized incidence and mortality rates to the world (WHO 2000-2025) and 2011 Canadian standard populations. Standardized incidence rate ratios (SRR) were calculated. Data were stratified by sex, year, and region. U.S. data were broken down by race [White; American Indian/Alaska Native (AIAN)]. Race data were not available from non-U.S. cancer registries., Results: Most populations showed declining incidence and mortality rates over time. Incidence rates among Greenland males and females, Alaska AIAN males and females, and Northern Canadian both sexes were elevated compared with regional counterparts and remained stable. The largest male SRR was observed among Alaska AIAN versus Alaska Whites [SRR = 3.82; 95% confidence interval (95% CI), 2.71-5.37]. The largest female SRR was observed among Alaska AIAN versus Alaska Whites (SRR = 4.10; 95% CI, 2.62-6.43)., Conclusions: Despite stomach cancer incidence and mortality rates declining overall, some northern and Indigenous populations experience elevated and stable incidence and mortality rates., Impact: There is a need to address disparities observed among circumpolar subpopulations. Given similarities in incidence, mortality, and risk factor prevalence across circumpolar regions, addressing disparities could benefit from coordinated international action., (©2021 American Association for Cancer Research.)

Background: Haemophilus influenzae bacteria can cause asymptomatic carriage and invasive disease. Haemophilus influenzae serotype a (Hia) is an emerging cause of invasive disease in Alaska, with greatest burden occurring among rural Alaska Native (AN) children. The first case of invasive Hia (iHia) in Alaska was reported in 2002; however, it is unclear how long the pathogen has been in Alaska., Methods: We quantified immunoglobulin G antibodies against Hia (anti-Hia) in 839 banked serum samples from Alaska residents, comparing antibody concentrations in samples drawn in the decades before (1980s and 1990s) and after (2000s) the emergence of iHia. We also assessed serum antibody concentration by age group, region of residence, and race., Results: The anti-Hia was >0.1 µg/mL in 88.1% (348 of 395) and 91.0% (404 of 444) of samples from the decades prior and after the emergence of Hia, respectively (P = .17). No significant differences in antibody levels were detected between people from rural and urban regions (1.55 vs 2.08 µg/mL, P = .91 for age ≥5) or between AN and non-AN people (2.50 vs 2.60 µg/mL, P = .26)., Conclusions: Our results are consistent with widespread Hia exposure in Alaska predating the first iHia case. No difference in Hia antibody prevalence was detected between populations with differing levels of invasive disease., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Objective: In the United States, HPV vaccination is routinely recommended at age 11 or 12 years; the series can be started at age 9. We conducted a cohort study to assess long-term immunogenicity of quadrivalent HPV vaccine (4vHPV) in an American Indian/Alaska Native (AI/AN) Indigenous population., Methods: During 2011-2014, we enrolled AI/AN girls and boys aged 9-14 years, who were vaccinated with a 3-dose series of 4vHPV. Serum specimens were collected at five time points: immediately prior to doses 2 and 3, and at one month, one year, and two years after series completion. Antibody testing was performed using a multiplex virus-like-particle-IgG ELISA for 4vHPV types (HPV 6/11/16/18)., Results: Among 477 children (405 girls/72 boys) completing the 3-dose series, median age at enrollment was 11.2 years. Of the 477, 72 (15%) were tested before dose 2 and 70 (15%) before dose 3. Following series completion, 435 (91%) were tested at one month, 382 (80%) at one year, and 351 (74%) at two years. All tested participants had detectable antibody to 4vHPV types at all time points measured. Geometric mean concentrations (GMCs) for 4vHPV types at one month and two years post-series completion were 269.9 and 32.7 AU/ml for HPV6, 349.3 and 42.9 AU/ml for HPV11, 1240.2 and 168.3 IU/ml HPV16, and 493.2 and 52.2 IU/ml for HPV18. Among children tested after each dose, GMCs after doses 1 and 2 were 3.9 and 32.2 AU/ml for HPV6, 5.3 and 45.6 AU/ml for HPV11, 20.8 and 187.9 IU/ml for HPV16; and 6.6 and 49.7 IU/ml for HPV18. No serious adverse events were reported., Conclusion: All AI/AN children developed antibodies to all 4vHPV types after vaccination. GMCs rose after each dose, then decreased to a plateau over the subsequent two years. This cohort will continue to be followed to determine duration of antibody response., 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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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.)

Objective: To assess whether a community water service is associated with the frequency of sugar-sweetened beverages (SSB) consumption, obesity, or perceived health status in rural Alaska., Design: We examined the cross-sectional associations between community water access and frequency of SSB consumption, body mass index categories, and perceived health status using data from the 2013 and 2015 Alaska Behavioral Risk Factor Surveillance System (BRFSS). Participants were categorized by zip code to 'in-home piped water service' or 'no in-home piped water service' based on water utility data. We evaluated the univariable and multivariable (adjusting for age, household income and education) associations between water service and outcomes using log-linear survey-weighted generalized linear models., Setting: Rural Alaska, USA., Subjects: Eight hundred and eighty-seven adults, aged 25 years and older., Results: In unadjusted models, participants without in-home water reported consuming SSB more often than participants with in-home water (1·46, 95 % CI: 1·06, 2·00). After adjustment for potential confounders, the effect decreased but remained borderline significant (1·29, 95 % CI: 1·00, 1·67). Obesity was not significantly associated with water service but self-reported poor health was higher in those communities without in-home water (1·63, 95 % CI: 1·05, 2·54)., Conclusions: Not having access to in-home piped water could affect behaviours surrounding SSB consumption and general perception of health in rural Alaska.

Introduction. Gastric cancer is a health disparity in the Alaska Native people. The incidence of Helicobacter pylori infection, a risk factor for non-cardia gastric adenocarcinoma, is also high. Gastric cancer is partially associated with the virulence of the infecting strain. Aim. To genotype the vacA s, m and i and cag pathogenicity island ( cagPAI ) genes in H. pylori from Alaskans and investigate associations with gastropathy. Methodology. We enrolled patients with gastritis, peptic ulcer disease (PUD) and intestinal metaplasia (IM) in 1998-2005 and patients with gastric cancer in 2011-2013. Gastric biopsies were collected and cultured and PCR was performed to detect the presence of the right and left ends of the cagPAI , the cagA , cagE , cagT and virD4 genes and to genotype the vacA s, m and i regions. Results. We recruited 263 people; 22 (8 %) had no/mild gastritis, 121 (46 %) had moderate gastritis, 40 (15%) had severe gastritis, 38 (14 %) had PUD, 30 (11 %) had IM and 12 (5 %) had gastric cancer. H. pylori isolates from 150 (57%) people had an intact cagPAI ; those were associated with a more severe gastropathy ( P ≤0.02 for all comparisons). H. pylori isolates from 77 % of people had either the vacA s1/i1/m1 (40 %; 94/234) or s2/i2/m2 (37 %; 86/234) genotype. vacA s1/i1/m1 was associated with a more severe gastropathy ( P ≤0.03 for all comparisons). Conclusions. In this population with high rates of gastric cancer, we found that just over half of the H. pylori contained an intact cagPAI and 40 % had the vacA s1/i1/m1 genotype. Infection with these strains was associated with a more severe gastropathy.

The risk for invasive streptococcal infection has not been clearly quantified among persons experiencing homelessness (PEH). We compared the incidence of detected cases of invasive group A Streptococcus infection, group B Streptococcus infection, and Streptococcus pneumoniae (pneumococcal) infection among PEH with that among the general population in Anchorage, Alaska, USA, during 2002-2015. We used data from the Centers for Disease Control and Prevention's Arctic Investigations Program surveillance system, the US Census, and the Anchorage Point-in-Time count (a yearly census of PEH). We detected a disproportionately high incidence of invasive streptococcal disease in Anchorage among PEH. Compared with the general population, PEH were 53.3 times as likely to have invasive group A Streptococcus infection, 6.9 times as likely to have invasive group B Streptococcus infection, and 36.3 times as likely to have invasive pneumococcal infection. Infection control in shelters, pneumococcal vaccination, and infection monitoring could help protect the health of this vulnerable group.

Background: Due to their close relationship with the environment, Alaskans are at risk for zoonotic pathogen infection. One way to assess a population's disease burden is to determine the seroprevalence of pathogens of interest. The objective of this study was to determine the seroprevalence of 11 zoonotic pathogens in people living in Alaska. Methods: In a 2007 avian influenza exposure study, we recruited persons with varying wild bird exposures. Using sera from this study, we tested for antibodies to Cryptosporidium spp., Echinococcus spp., Giardia intestinalis , Toxoplasma gondii , Trichinella spp., Brucella spp., Coxiella burnetii , Francisella tularensis , California serogroup bunyaviruses, and hepatitis E virus (HEV). Results: Eight hundred eighty-seven persons had sera tested, including 454 subsistence bird hunters and family members, 160 sport bird hunters, 77 avian wildlife biologists, and 196 persons with no wild bird exposure. A subset ( n  = 481) of sera was tested for California serogroup bunyaviruses. We detected antibodies to 10/11 pathogens. Seropositivity to Cryptosporidium spp. (29%), California serotype bunyaviruses (27%), and G. intestinalis (19%) was the most common; 63% (301/481) of sera had antibodies to at least one pathogen. Using a multivariable logistic regression model, Cryptosporidium spp. seropositivity was higher in females (35.7% vs. 25.0%; p  = 0.01) and G . intestinalis seropositivity was higher in males (21.8% vs. 15.5%; p  = 0.02). Alaska Native persons were more likely than non-Native persons to be seropositive to C. burnetii (11.7% vs. 3.8%; p  = 0.005) and less likely to be seropositive to HEV (0.4% vs. 4.1%; p  = 0.01). Seropositivity to Cryptosporidium spp., C. burnetii , HEV, and Echinococcus granulosus was associated with increasing age ( p  ≤ 0.01 for all) as was seropositivity to ≥1 pathogen ( p  < 0.0001). Conclusion: Seropositivity to zoonotic pathogens is common among Alaskans with the highest to Cryptosporidium spp., California serogroup bunyaviruses, and G. intestinalis . This study provides a baseline for use in assessing seroprevalence changes over time.

Hepatitis C virus (HCV) infection in pregnant women is of concern as it presents a health threat not only to the mother, but also to her infant. A retrospective analysis was performed to evaluate HCV testing and exposure in women who delivered infants between 2013 and 2016 at a referral hospital in Alaska. Multiple risk behaviors were evaluated, including drug dependency or abuse (drug abuse), tobacco use, alcohol dependency or abuse, and late presentation to prenatal care. Of the 2856 women who delivered between 2013 and 2016, 470 (16.5%) were tested for HCV during pregnancy and 1356 (47.5%) were tested at any time prior to delivery (including pregnancy); 62 (2.2%) were positive for HCV antibodies. Of the 162 women with a documented history of drug abuse, 95 (58.6%) were tested for HCV during pregnancy and 143 (88.3%) were tested at any time prior to delivery (including pregnancy); 30 (18.5%) were positive for HCV antibodies. Forty-nine women (34%) with a documented history of drug abuse who were not previously known to be HCV positive were not tested for HCV during their pregnancy. In conclusion, approximately 2% of pregnant women in the study population were known to have been exposed to HCV by the time of their delivery. One-third of women with documented drug abuse did not have an HCV test during pregnancy, revealing gaps in HCV testing of pregnant women. Further studies are needed to understand the full costs and benefits of risk-based screening versus universal screening in this and other populations.

Helicobacter pylori infection is common among Alaska native (AN) people, however scant gastric histopathologic data is available for this population. This study aimed to characterise gastric histopathology and H. pylori infection among AN people. We enrolled AN adults undergoing upper endoscopy. Gastric biopsy samples were evaluated for pathologic changes, the presence of H. pylori, and the presence of cag pathogenicity island-positive bacteria. Of 432 persons; two persons were diagnosed with gastric adenocarcinoma, two with MALT lymphoma, 40 (10%) with ulcers, and 51 (12%) with intestinal metaplasia. Fifty-five per cent of H. pylori-positive persons had cag pathogenicity island positive bacteria. The gastric antrum had the highest prevalence of acute and chronic moderate-severe gastritis. H. pylori-positive persons were 16 and four times more likely to have moderate-severe acute gastritis and chronic gastritis (p < 0.01), respectively. An intact cag pathogenicity island positive was correlated with moderate-severe acute antral gastritis (53% vs. 31%, p = 0.0003). H. pylori-positive persons were more likely to have moderate-severe acute and chronic gastritis compared to H. pylori-negative persons. Gastritis and intestinal metaplasia were most frequently found in the gastric antrum. Intact cag pathogenicity island positive was correlated with acute antral gastritis and intestinal metaplasia.

We identified risk factors for any emm type group A streptococcal (GAS) colonization while investigating an invasive emm26.3 GAS outbreak among people experiencing homelessness in Alaska. Risk factors included upper extremity skin breakdown, sleeping outdoors, sharing blankets, and infrequent tooth brushing. Our results may help guide control efforts in future outbreaks.

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.)

Giardia duodenalis and Cryptosporidium spp. are common intestinal protozoa that can cause diarrhoeal disease. Although cases of infection with Giardia and Cryptosporidium have been reported in Alaska, the seroprevalence and correlates of exposure to these parasites have not been characterised. We conducted a seroprevalence survey among 887 residents of Alaska, including sport hunters, wildlife biologists, subsistence bird hunters and their families and non-exposed persons. We tested serum using a multiplex bead assay to evaluate antibodies to the Giardia duodenalis variant-specific surface protein conserved structural regions and to the Cryptosporidium parvum 17- and 27-kDa antigens. Approximately one third of participants in each group had evidence of exposure to Cryptosporidium. Prevalence of Giardia antibody was highest among subsistence hunters and their families (30%), among whom positivity was associated with lack of community access to in-home running water (adjusted prevalence ratio [aPR] 1.15, 95% confidence interval (CI) 1.02-1.28) or collecting rain, ice, or snow to use as drinking water (aPR 1.09, 95% CI 1.01-1.18). Improving in-home water access for entire communities could decrease the risk of exposure to Giardia.

Background: Invasive infections from Haemophilus influenzae serotype a (Hia) have been reported with increasing frequency, especially among indigenous populations. However, there are limited population-based studies of clinical severity. We studied invasive Hia infections in Alaska to determine clinical characteristics, mortality and sequelae., Methods: We defined an invasive Hia infection as the first detection of Hia from a usually sterile site in a child <10 years of age from Alaska. We identified cases using the Alaska Invasive Bacterial Diseases Surveillance System and reviewed medical charts up to 2 years after reported illness., Results: We identified invasive Hia infections in 36 children, 28 (78%) <1 year old, 34 (94%) living in an Alaskan village and 25 (69%) without documented underlying illness. Overlapping clinical presentations included meningitis in 15 children (42%); bacteremia and pneumonia in 10 children (28%); and bone, joint or soft tissue infections in 10 children (22%). In 4 other children, no source of invasive infection was identified. Intensive care was provided for 11 children (31%); 12 children (33%) required surgical intervention. One year after infection, 4 children (11%) had died from Hia, and 5 children (14%) had ongoing neurologic sequelae., Conclusions: Invasive Hia infections in Alaska occurred predominantly in Alaska Native infants in rural communities. Although one-third of children had preexisting conditions, most cases occurred without known comorbidity. Clinical syndromes were frequently severe. One year after infection, 1 in 4 children had either died or had neurologic sequelae. An effective vaccine would prevent significant morbidity and mortality in affected populations.

Background: In 2016, we detected an outbreak of group A Streptococcus (GAS) invasive infections among the estimated 1000 persons experiencing homelessness (PEH) in Anchorage, Alaska. We characterized the outbreak and implemented a mass antibiotic intervention at homeless service facilities., Methods: We identified cases through the Alaska GAS laboratory-based surveillance system. We conducted emm typing, antimicrobial susceptibility testing, and whole-genome sequencing on all invasive isolates and compared medical record data of patients infected with emm26.3 and other emm types. In February 2017, we offered PEH at 6 facilities in Anchorage a single dose of 1 g of azithromycin. We collected oropharyngeal and nonintact skin swabs on a subset of participants concurrent with the intervention and 4 weeks afterward., Results: From July 2016 through April 2017, we detected 42 invasive emm26.3 cases in Anchorage, 35 of which were in PEH. The emm26.3 isolates differed on average by only 2 single-nucleotide polymorphisms. Compared to other emm types, infection with emm26.3 was associated with cellulitis (odds ratio [OR], 2.5; P = .04) and necrotizing fasciitis (OR, 4.4; P = .02). We dispensed antibiotics to 391 PEH. Colonization with emm26.3 decreased from 4% of 277 at baseline to 1% of 287 at follow-up (P = .05). Invasive GAS incidence decreased from 1.5 cases per 1000 PEH/week in the 6 weeks prior to the intervention to 0.2 cases per 1000 PEH/week in the 6 weeks after (P = .01)., Conclusions: In an invasive GAS outbreak in PEH in Anchorage, mass antibiotic administration was temporally associated with reduced invasive disease cases and colonization prevalence.

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: We describe the relative impact of the heptavalent pneumococcal conjugate vaccine (PCV7, introduced 2001) and antibiotic use on colonization by antibiotic-resistant pneumococci in urban Alaskan children during 2000-2010., Methods: We obtained nasopharyngeal swab specimens from a convenience sample of children aged <5 years at clinics annually during 2000-2004 and 2008-2010. PCV7 status and antibiotic use <90 days before enrollment were determined by interview/medical records review. Pneumococci were characterized by serotype and susceptibility to penicillin (PCN). Isolates with full PCN resistance (PCN-R) or intermediate PCN resistance (PCN-I) were classified as PCN-NS., Results: We recruited 3496 children (median, 452 per year). During 2000-2010, a range of 18-29% per year of children used PCN/amoxicillin (P value for trend = 0.09); the proportion age-appropriately vaccinated with PCV7 increased (0[FIGURE DASH]90%; P < 0.01). Among pneumococcal isolates, the PCV7-serotype proportion decreased (53-<1%; P < 0.01) and non[FIGURE DASH]PCV7-serotype proportion increased (43-95%; P < 0.01). PCN-R pneumococcal colonization prevalence decreased (23-9%; P < 0.01) and PCN-I pneumococcal colonization prevalence increased (13-24%; P < 0.01); overall PCN-NS pneumococcal colonization prevalence was unchanged. PCN-NS among colonizing PCV7-type and non[FIGURE DASH]PCV7-type pneumococci remained unchanged; a mean of 31% per year of PCV7-type and 10% per year of non[FIGURE DASH]PCV7-type isolates were PCN-R, and 10% per year of PCV7 and 20% per year of non[FIGURE DASH]PCV7-type isolates were PCN-I., Conclusions: Overall, PCN-NS pneumococcal colonization remained unchanged during 2000-2010 because increased colonization by predominantly PCN-I non-PCV7 serotypes offset decreased colonization by predominantly PCN-R PCV7 serotypes. Proportion PCN-NS did not increase within colonizing pneumococcal serotype groups (PCV7 vs. non-PCV7) despite stable PCN use in our population.

Background: Alaska Native (AN) children have experienced high rates of invasive pneumococcal disease (IPD). In March 2010, PCV13 was introduced statewide in Alaska. We evaluated the impact of PCV13 on IPD in children and adults, 45 months after introduction., Methods: Pneumococcal sterile site isolates, reported through state-wide surveillance, were serotyped using standard methods. We defined a pre-PCV13 time period 2005-2008 and post-PCV13 time period April 2010-December 2013; excluding Jan 2009-March 2010 because PCV13 was introduced pre-licensure in one high-risk region in 2009., Results: Among Alaska children <5 years, PCV13 serotypes comprised 65% of IPD in the pre-PCV13 period and 26% in the PCV13 period. Among all Alaska children <5 years, IPD rates decreased from 60.9 (pre) to 25.4 (post) per 100,000/year (P<0.001); PCV13 serotype IPD decreased from 37.7 to 6.4 (P<0.001). Among AN children <5 years, IPD rates decreased from 149.2 to 60.8 (P<0.001); PCV13 serotype IPD decreased from 87.0 to 17.4 (P<0.001); non-PCV13 serotype IPD did not change significantly. Among persons 5-17 and ≥45 years, the post-vaccine IPD rate was similar to the baseline period, but declined in persons 18-44 years (39%, P<0.001); this decline was similar in AN and non-AN persons (38%, P=0.016, 43%, P=0.014, respectively)., Conclusions: Forty-five months after PCV13 introduction, overall IPD and PCV13-serotype IPD rates had decreased 58% and 83%, respectively, in Alaska children <5 years of age when compared with 2005-2008. We observed evidence of indirect effect among adults with a 39% reduction in IPD among persons 18-44 years., (Published by Elsevier Ltd.)

We performed a study to determine rates of reinfection in three groups followed for 2 years after successful treatment: American Indian/Alaska Native (AI/AN) persons living in urban (group 1) and rural (group 2) communities, and urban Alaska non-Native persons (group 3). We enrolled adults diagnosed with H. pylori infection based on a positive urea breath test (13C-UBT). After successful treatment was documented at 2 months, we tested each patient by 13C-UBT at 4, 6, 12 and 24 months. At each visit, participants were asked about medication use, illnesses and risk factors for reinfection. We followed 229 persons for 2 years or until they became reinfected. H. pylori reinfection occurred in 36 persons; cumulative reinfection rates were 14·5%, 22·1%, and 12·0% for groups 1, 2, and 3, respectively. Study participants who became reinfected were more likely to have peptic ulcer disease (P = 0·02), low education level (P = 0·04), or have a higher proportion of household members infected with H. pylori compared to participants who did not become reinfected (P = 0·03). Among all three groups, reinfection occurred at rates higher than those reported for other US populations (<5% at 2 years); rural AI/AN individuals appear to be at highest risk for reinfection.

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.

Background: In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced a 7-valent vaccine (PCV7) that contained all PCV7 serotypes plus 6 additional serotypes (PCV6+). We conducted annual surveys from 2008 to 2012 to determine the effect of PCV13 on colonization by pneumococcal serotypes., Methods: We obtained nasopharyngeal swabs for pneumococcal identification and serotyping from residents of all ages at 8 rural villages and children age <60 months at 2 urban clinics. We conducted interviews/medical records review for all participants., Results: A total of 18 207 nasopharyngeal swabs (rural = 16 098; urban = 2109) were collected. From 2008 to 2012, 84% of rural and 90% of urban children age <5 years were age-appropriately vaccinated with a PCV. Overall pneumococcal colonization prevalence remained stable among rural (66%) and urban (35%) children age <5 years, and adults age ≥18 years (14%). Colonization by PCV6+ serotypes declined significantly among rural children age <5 years, urban children age <5, and adults age ≥18 over the course of the study (25%-5%, 22%-9%, 22%-6%, respectively)., Conclusions: PCV13 was rapidly introduced into the Alaska childhood immunization schedule and reduced colonization by PCV6+ serotypes among children. Unvaccinated adults also experienced comparable reductions in vaccine serotype colonization indicating substantial indirect protection from PCV13.

Introduction: Alaska Native colorectal cancer (CRC) incidence and mortality rates are the highest of any ethnic/racial group in the United States. CRC screening using guaiac-based fecal occult blood tests (gFOBT) are not recommended for Alaska Native people because of false-positive results associated with a high prevalence of Helicobacter pylori-associated hemorrhagic gastritis. This study evaluated whether the newer immunochemical FOBT (iFOBT) resulted in a lower false-positive rate and higher specificity for detecting advanced colorectal neoplasia than gFOBT in a population with elevated prevalence of H. pylori infection., Methods: We used a population-based sample of 304 asymptomatic Alaska Native adults aged 40 years or older undergoing screening or surveillance colonoscopy (April 2008-January 2012)., Results: Specificity differed significantly (P < .001) between gFOBT (76%; 95% CI, 71%-81%) and iFOBT (92%; 95% CI, 89%-96%). Among H. pylori-positive participants (54%), specificity of iFOBT was even higher (93% vs 69%). Overall, sensitivity did not differ significantly (P = .73) between gFOBT (29%) and iFOBT (36%). Positive predictive value was 11% for gFOBT and 32% for iFOBT., Conclusion: The iFOBT had a significantly higher specificity than gFOBT, especially in participants with current H. pylori infection. The iFOBT represents a potential strategy for expanding CRC screening among Alaska Native and other populations with elevated prevalence of H. pylori, especially where access to screening endoscopy is limited.

Background: American Indian/Alaska Native (AI/AN) people suffer substantially higher rates of invasive pneumococcal disease (IPD) than the general US population. We evaluated antimicrobial prescribing data and their association with non-susceptibility in Streptococcus pneumoniae causing IPD in AI/AN people between 1992 and 2009., Methods: Antimicrobial use data were gathered from the electronic patient management system and included all prescriptions dispensed to Alaska Native patients aged 5 years and older from outpatient pharmacies at the Alaska Native Medical Center (ANMC). Antimicrobial susceptibility data were gathered from pneumococcal isolates causing IPD among Anchorage Service Unit AI/AN residents aged 5 years and older. Data were restricted to serotypes not contained in the pneumococcal vaccine (PCV7)., Results: Over the study period, overall antimicrobial prescribing increased 59% (285/1,000 persons/year in 1992 to 454/1,000 persons per year in 2009, p<0.001). Trimethoprim/sulfamethoxazole prescribing increased (43/1,000 persons/year in 1992 to 108/1,000 persons/year in 2009, p<0.001) and non-susceptibility to trimethoprim/sulfamethoxazole in AI/AN patients ≥5 years of age increased in non-PCV7 serotypes (0-12%, p<0.05). Similarly, prescribing rates increased for macrolide antibiotics (46/1,000 persons/year in 1992 to 84/1,000 persons/year in 2009, p<0.05). We observed no statistically significant change over time in erythromycin non-susceptibility among non-PCV7 serotypes in AI/AN patients aged 5 years or greater (0-7%, p=0.087)., Conclusion: Antimicrobial prescribing patterns of some antibiotics in the AI/AN population corresponded to increased antimicrobial resistance in clinical isolates. This study highlights the on-going threat of antimicrobial resistance, the critical importance of judicious prescribing of antibiotics and the potential utility of prescribing data for addressing this issue.

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: After the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in Alaska, the incidence of invasive pneumococcal disease (IPD) due to non-vaccine serotypes, particularly serotype 19A, increased. The aim of this study was to describe the molecular epidemiology of IPD due to serotype 19A in Alaska., Methods: IPD data were collected from 1986 to 2010 through population-based laboratory surveillance. Isolates were serotyped by the Quellung reaction and MICs determined by broth microdilution. Genotypes were assessed by multilocus sequence typing., Results: Among 3,294 cases of laboratory-confirmed IPD, 2,926 (89%) isolates were available for serotyping, of which 233 (8%) were serotype 19A. Across all ages, the proportion of IPD caused by serotype 19A increased from 3.5% (63/1823) pre-PCV7 (1986-2000) to 15.4% (170/1103) post-PCV7 (2001-2010) (p < 0.001); among children < 5 years of age, the proportion increased from 5.0% (39/776) to 33.0% (76/230) (p < 0.001). The annual incidence rate of IPD due to serotype 19A (all ages) increased from 0.73 cases pre-PCV7 to 2.56 cases/100,000 persons post-PCV7 (p < 0.001); rates among children < 5 years of age increased from 4.84 cases to 14.1 cases/100,000 persons (p < 0.001). Among all IPD isolates with reduced susceptibility to penicillin, 17.8% (32/180) were serotype 19A pre-PCV7 and 64% (121/189) were serotype 19A post-PCV7 (p < 0.001). Eighteen different sequence types (STs) were identified; ST199 or single locus variants of ST199 (n = 150) and ST172 (n = 59) accounted for the majority of isolates. Multidrug-resistant isolates were clustered in ST199 and ST320., Conclusion: While PCV13 should significantly reduce the burden of disease due to 19A, these data highlight the need to continue surveillance for IPD to monitor the effects of vaccination on the expansion and emergence of non-PCV strains.

Objectives: To examine the epidemiology of infectious disease (ID) hospitalisations among Alaska Native (AN) people., Methods: Hospitalisations with a first-listed ID diagnosis for American Indians and ANs residing in Alaska during 2001-2009 were selected from the Indian Health Service direct and contract health service inpatient data. ID hospitalisations to describe the general US population were selected from the Nationwide Inpatient Sample. Annual and average annual (2007-2009) hospitalization rates were calculated., Results: During 2007-2009, IDs accounted for 20% of hospitalisations among AN people. The 2007-2009 average annual age-adjusted ID hospitalisation rate (2126/100,000 persons) was higher than that for the general US population (1679/100,000; 95% CI 1639-1720). The ID hospitalisation rate for AN people increased from 2001 to 2009 (17%, p < 0.001). Although the rate during 2001-2009 declined for AN infants (< 1 year of age; p = 0.03), they had the highest 2007-2009 average annual rate (15106/100,000), which was 3 times the rate for general US infants (5215/100,000; 95% CI 4783-5647). The annual rates for the age groups 1-4, 5-19, 40-49, 50-59 and 70-79 years increased (p < 0.05). The highest 2007-2009 age-adjusted average annual ID hospitalisation rates were in the Yukon-Kuskokwim (YK) (3492/100,000) and Kotzebue (3433/100,000) regions; infant rates were 30422/100,000 and 26698/100,000 in these regions, respectively. During 2007-2009, lower respiratory tract infections accounted for 39% of all ID hospitalisations and approximately 50% of ID hospitalisations in YK, Kotzebue and Norton Sound, and 74% of infant ID hospitalisations., Conclusions: The ID hospitalisation rate increased for AN people overall. The rate for AN people remained higher than that for the general US population, particularly in infants and in the YK and Kotzebue regions. Prevention measures to reduce ID morbidity among AN people should be increased in high-risk regions and for diseases with high hospitalisation rates.

Before introduction of Haemophilus influenzae type b (Hib) vaccines, rates of Hib disease in Alaska's indigenous people were among the highest in the world. Vaccination reduced rates dramatically; however, invasive H. influenzae type a (Hia) disease has emerged. Cases of invasive disease were identified through Alaska statewide surveillance during 1983-2011. Of 866 isolates analyzed for serotype, 32 (4%) were Hia. No Hia disease was identified before 2002; 32 cases occurred during 2002-2011 (p<0.001). Median age of case-patients was 0.7 years; 3 infants died. Incidence of Hia infection (2002-2011) among children <5 years was 5.4/100,000; 27 cases occurred in Alaska Native children (18/100,000) versus 2 cases in non-Native children (0.5/100,000) (risk ratio = 36, p<0.001). From 12/2009 to 12/2011, 15 cases of Hia disease occurred in southwestern Alaska (in children <5 years, rate = 204/100,000). Since introduction of the Hib conjugate vaccine, Hia infection has become a major invasive bacterial disease in Alaska Native children.

Outbreaks of invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae serotype 12F were observed in two neighboring regions of rural Alaska in 2003 to 2006 and 2006 to 2008. IPD surveillance data from 1986 to 2009 and carriage survey data from 1998 to 2004 and 2008 to 2009 were reviewed to identify patterns of serotype 12F transmission. Pulsed-field gel electrophoresis was performed on all available isolates, and selected isolates were characterized by additional genetic subtyping methods. Serotype 12F IPD occurred in two waves in Alaska between 1986 and 2008. While cases of disease occurred nearly every year in Anchorage, in rural regions, 12F IPD occurred with rates 10- to 20-fold higher than those in Anchorage, often with many years between disease peaks and generally caused by a single predominant genetic clone. Carriage occurred predominantly in adults, except early in the rural outbreaks, when most carriage was in persons <18 years old. In rural regions, carriage of 12F disappeared completely after outbreaks. Different 12F clones appear to have been introduced episodically into rural populations, spread widely in young, immunologically naïve populations (leading to outbreaks of IPD lasting 1 to 3 years), and then disappeared rapidly from the population. Larger population centers might have been the reservoir for these clones. This epidemiologic pattern is consistent with a highly virulent, but immunogenic, form of pneumococcus.

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.

Objectives: Treatment with pegylated interferon and ribavirin may prevent progression of liver disease among patients with chronic hepatitis C virus infection (HCV). Treatment initiation is based on published clinical eligibility criteria, patients' willingness to undergo treatment and likelihood of success. We examined treatment eligibility in a cohort of Alaska Native and American Indian persons with chronic HCV infection., Study Design: Retrospective cohort study., Methods: Medical records of all treatment naïve HCV RNA positive patients given an appointment by hepatology specialty clinic staff in 2003 and 2007 were evaluated by a hepatology provider to investigate documented reasons for treatment deferral., Results: Treatment was initiated in 4 of 94 patients (4%) in 2003 and 14 of 146 patients (10%) in 2007. Major reasons for treatment deferral in 2003 versus 2007 included inconsistent appointment attendance (36% of deferrals vs. 18%), active substance abuse (17% vs. 22%), patient decision (17% vs. 27%), liver biopsy without fibrosis or normal ALT (8% vs. 3%), uncontrolled psychiatric condition (7% vs. 7%) and concurrent medical condition (6% vs. 9%). There was significant improvement in proportion of appointments attended in 2007 versus 2003 (76% vs. 67%, p = 0.04) and the percentage of patients attending at least 1 appointment (84% vs. 66%, p = 0.002)., Conclusions: Multiple reasons for treatment deferral were documented. Despite a significant improvement in hepatology clinic attendance and an increase in the number of patients started on treatment in 2007 compared to 2003, the overall percentage of those treated remained low.

Aim: To evaluate the accuracy of two non-invasive tests in a population of Alaska Native persons. High rates of Helicobacter pylori (H. pylori) infection, H. pylori treatment failure, and gastric cancer in this population necessitate documentation of infection status at multiple time points over a patient's life., Methods: In 280 patients undergoing endoscopy, H. pylori was diagnosed by culture, histology, rapid urease test, (13)C urea breath test (UBT), and immunoglobulin G antibodies to H. pylori in serum. The performances of (13)C-UBT and antibody test were compared to a gold standard defined by a positive H. pylori test by culture or, in case of a negative culture result, by positive histology and a positive rapid urease test., Results: The sensitivity and specificity of the (13)C-UBT were 93% and 88%, respectively, relative to the gold standard. The antibody test had an equivalent sensitivity of 93% with a reduced specificity of 68%. The false positive results for the antibody test were associated with previous treatment for an H. pylori infection [relative risk (RR) = 2.8]. High levels of antibodies to H. pylori were associated with chronic gastritis and male gender, while high scores in the (13)C-UBT test were associated with older age and with the H. pylori bacteria load on histological examination (RR = 4.4)., Conclusion: The (13)C-UBT outperformed the antibody test for H. pylori and could be used when a non-invasive test is clinically necessary to document treatment outcome or when monitoring for reinfection.

Helicobacter pylori infection is more common in Alaska Native persons than in the general U.S. population, with seroprevalence to H. pylori approaching 75%. Previous studies in Alaska have demonstrated elevated proportions of antimicrobial resistance among H. pylori isolates. We analyzed H. pylori data from the Centers for Disease Control and Prevention's sentinel surveillance in Alaska from January 2000 to December 2008 to determine the proportion of culture-positive biopsy specimens with antimicrobial resistance from Alaska Native persons undergoing endoscopy. The aim of the present study was to monitor antimicrobial resistance of H. pylori isolates over time and by region in Alaska Native persons. Susceptibility testing of H. pylori isolates to metronidazole, clarithromycin, amoxicillin, and tetracycline was performed using agar dilution. Susceptibility testing for levofloxacin was performed by Etest. Overall, 45% (532/1,181) of persons undergoing upper endoscopy were culture positive for H. pylori. Metronidazole resistance was demonstrated in isolates from 222/531 (42%) persons, clarithromycin resistance in 159/531 (30%) persons, amoxicillin resistance in 10/531 (2%) persons, and levofloxacin resistance in 30/155 (19%) persons; no tetracycline resistance was documented. The prevalence of metronidazole, clarithromycin, and levofloxacin resistance varied by region. Female patients were more likely than male patients to demonstrate metronidazole (P < 0.05) and clarithromycin (P < 0.05) resistance. No substantial change in the proportion of persons with resistant isolates was observed over time. Resistance to metronidazole, clarithromycin, and levofloxacin is more common among H. pylori isolates from Alaska Native persons than those from elsewhere in the United States.

The International Circumpolar Surveillance (ICS) Program was initiated in 1999 to conduct population-based surveillance for invasive pneumococcal disease in select regions of the Arctic. An interlaboratory quality control (QC) program for pneumococcal serotyping and antibiotic susceptibility testing was incorporated into ICS by reference laboratories in northern Canada (Laboratoire de Santé Publique du Québec [LSPQ] in Sainte-Anne de Bellevue, Québec; National Centre for Streptococcus [NCS] in Edmonton, Alberta) and Alaska (Arctic Investigations Program [AIP]). The World Health Organization's Collaborating Centre for Reference and Research on Pneumococci at the Statens Serum Institute (SSI) in Copenhagen, Denmark, joined the QC program in 2004. The Iceland Reference Laboratory (IRL) in Reykjavik, Iceland, joined the QC program in 2006, but due to small sample sizes, data from IRL are not included in this report. From 1999 through 2008, 190 isolates were distributed among four laboratories (AIP, NCS, LSPQ, and SSI). The overall serotype concordance was 95.8%, and the overall serogroup concordance was 97.4%. The overall modal MIC concordance for testing by broth microdilution (BMD) and agar dilution was >96% for all the antibiotics except erythromycin (92.1%) and clindamycin (89.5%). MIC comparisons between the Etest and BMD resulted in lower concordance for erythromycin (73.9%), clindamycin (65.5%), and trimethoprim-sulfamethoxazole (80%); however, categorical concordance (susceptible, resistant) remained high at 98.6%, 89.1%, and 90.9%, respectively. Our data demonstrate a high degree of correlation of serotyping and antimicrobial susceptibility testing results between four participating laboratories.

Alaska Native people have suffered disproportionately from previous influenza pandemics. We evaluated 3 separate syndromic data sources to determine temporal and geographic patterns of spread of 2009 pandemic influenza A H1N1 (pH1N1) in Alaska, and reviewed records from persons hospitalized with pH1N1 disease in 3 areas in Alaska to characterize clinical and epidemiologic features of disease in Alaskans. A wave of pH1N1 disease swept through Alaska beginning in most areas in August or early September. In rural regions, where Alaska Native people comprise a substantial proportion of the population, disease occurred earlier than in other regions. Alaska Native people and Asian/Pacific Islanders (A/PI) were 2-4 times more likely to be hospitalized than whites. Alaska Native people and other minorities remain at high risk for early and substantial morbidity from pandemic influenza episodes. These findings should be integrated into plans for distribution and use of vaccine and antiviral agents.

Background: Various factors influence the development and rate of fibrosis progression in chronic hepatitis C virus (HCV) infection., Objectives: To examine factors associated with fibrosis in a longterm outcomes study of Alaska Native/American Indian persons who underwent liver biopsy, and to examine the rate of fibrosis progression in persons with subsequent biopsies., Methods: A cross-sectional analysis of the demographic, inflammatory and viral characteristics of persons undergoing liver biopsy compared individuals with early (Ishak fibrosis score of lower than 3) with those with advanced (Ishak score of 3 or greater) fibrosis. Persons who underwent two or more biopsies were analyzed for factors associated with fibrosis progression., Results: Of 253 HCV RNA-positive persons who underwent at least one liver biopsy, 76 (30%) had advanced fibrosis. On multivariate analysis, a Knodell histological activity index score of 10 to 14 and an alpha-fetoprotein level of 8 ng/mL or higher were found to be independent predictors of advanced liver fibrosis (P<0.0001 for each). When surrogate markers of liver inflammation (alanine aminotransferase, aspartate aminotransferase/alanine aminotransferase ratio and alpha-fetoprotein) were removed from the model, type 2 diabetes mellitus (P=0.001), steatosis (P=0.03) and duration of HCV infection by 10-year intervals (P=0.02) were associated with advanced fibrosis. Among 52 persons who underwent two or more biopsies a mean of 6.2 years apart, the mean Ishak fibrosis score increased between biopsies (P=0.002), with progression associated with older age at initial biopsy and HCV risk factors., Conclusions: The presence of type 2 diabetes mellitus, steatosis and duration of HCV infection were independent predictors of advanced fibrosis in the present cohort, with significant fibrosis progression demonstrated in persons who underwent serial biopsies.