Search

The International Circumpolar Surveillance System is a population-based surveillance network for invasive bacterial disease in the Arctic. The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced for routine infant vaccination in Alaska (2001), northern Canada (2002-2006), and Norway (2006). Data for invasive pneumococcal disease (IPD) were analyzed to identify clinical findings, disease rates, serotype distribution, and antimicrobial drug susceptibility; 11,244 IPD cases were reported. Pneumonia and bacteremia were common clinical findings. Rates of IPD among indigenous persons in Alaska and northern Canada were 43 and 38 cases per 100,000 population, respectively. Rates in children <2 years of age ranged from 21 to 153 cases per 100,000 population. In Alaska and northern Canada, IPD rates in children <2 years of age caused by PCV7 serotypes decreased by >80% after routine vaccination. IPD rates are high among indigenous persons and children in Arctic countries. After vaccine introduction, IPD caused by non-PCV7 serotypes increased in Alaska. [ABSTRACT FROM AUTHOR]

Before the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, rates of invasive H. influenzae disease among indigenous people of the North American Arctic were among the highest in the world. Routine vaccination reduced rates to low levels; however, serotype replacement with non-type b strains may result in a reemergence of invasive disease in children. We reviewed population-based data on invasive H. influenzae in Alaska and northern Canada from 2000-2005; 138 cases were reported. Among 88 typeable isolates, 42 (48%) were H. influenzae type a (Hia); 35 (83%) occurred in indigenous peoples. Among Hia patients, median age was 1.1 years; 62% were male; 1 adult died. Common clinical manifestations included meningitis, pneumonia, and septic arthritis. Overall annual incidence was 0.9 cases per 100,000 population. Incidence among indigenous children <2 years of age in Alaska and northern Canada was 21 and 102, respectively. Serotype a is now the most common H. influenzae serotype in the North American Arctic; the highest rates are among indigenous children. [ABSTRACT FROM AUTHOR]

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: Evidence suggests an increased risk of new-onset diabetes following COVID-19 infection. American Indian/Alaska Native (AI/AN) people were disparately impacted by the COVID-19 pandemic and historically have had higher diabetes incidence than other racial/ethnic groups in the US. We measured the association between COVID-19 infection and incident diabetes in AI/AN people., Methods: We conducted a retrospective cohort study using de-identified patient data from the Indian Health Service's (IHS) National Patient Information Reporting System. We estimated age-adjusted diabetes incidence rates, incidence rate ratios, and adjusted hazard ratios among three cohorts spanning pre-pandemic (1/1/2018-2/28/2020) and pandemic (3/1/2020-12/31/2021) timeframes: 1) pre-pandemic cohort (1,503,085 individuals); 2) no-COVID-19 pandemic cohort (1,344,339 individuals); and 3) COVID-19 cohort (176,483 individuals)., Findings: The COVID-19 cohort had an increased hazard of diabetes compared to the no-COVID-19 group (adjusted hazard ratio (aHR) = 1.56; 95% CI: 1.50-1.62) and the pre-pandemic group (aHR = 1.27; 95% CI: 1.22-1.32). The association between COVID-19 infection and new-onset diabetes was stronger in those with severe COVID-19 illness. A sensitivity analysis comparing the COVID-19 cohort to members of other cohorts that had acute upper respiratory infections showed an attenuated but higher risk of new-onset diabetes in those with COVID-19., Interpretation: AI/AN people diagnosed with COVID-19 had an elevated risk of a new diabetes diagnosis when compared to the no-COVID-19 group and the pre-pandemic group. The increased diabetes risk in the COVID-19 group remained in a sensitivity analysis that limited the comparator groups to individuals with an AURI diagnosis., Funding: US National Institute of Diabetes and Digestive and Kidney Diseases., Competing Interests: The authors declare no potential conflicts of interest relevant to this work., (© 2024 The Authors.)

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 and Aims: The duration of protection from hepatitis B vaccination in children and adults is not known. In 1981, we used three doses of plasma-derived hepatitis B vaccine to immunize a cohort of 1578 Alaska Native adults and children from 15 Alaska communities who were ≥6 months old., Approach and Results: We tested persons for antibody to hepatitis B surface antigen (anti-HBs) levels 35 years after receiving the primary series. Those with levels <10 mIU/ml received one booster dose of recombinant hepatitis B vaccine 2-4 weeks later and were then evaluated on the basis of anti-HBs measurements 30 days postbooster. Among the 320 recruited, 112 persons had not participated in the 22- or 30-year follow-up study (group 1), and 208 persons had participated but were not given an HBV booster dose (group 2). Among the 112 persons in group 1 who responded to the original primary series, 53 (47.3%) had an anti-HBs level ≥10 mIU/ml. Among group 1, 73.7% (28 of 38) of persons available for a booster dose responded to it with an anti-HBs level ≥10 mIU/ml at 30 days. Initial anti-HBs level after the primary series was correlated with higher anti-HBs levels at 35 years. Among 8 persons who tested positive for antibody to hepatitis B core antigen, none tested positive for HBsAg or HBV DNA., Conclusions: Based on anti-HBs level ≥10 mIU/ml at 35 years and a 73.7% booster dose response, we estimate that 86% of participants had evidence of protection 35 years later. Booster doses are not needed in the general population at this time., (© 2022 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of 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: The incidence of invasive disease caused by group A streptococcus (GAS) has increased in multiple countries in the past 15 years. However, despite these reports, to the best of our knowledge, no systematic reviews and combined estimates of the incidence of invasive GAS have been done in key high-risk groups. To address this, we estimated the incidence of invasive GAS disease, including death and disability outcomes, among two high-risk groups-namely, pregnant women and children younger than 5 years., Methods: We did a systematic review and meta-analyses on invasive GAS outcomes, including incidence, case fatality risks, and neurodevelopmental impairment risk, among pregnant women, neonates (younger than 28 days), infants (younger than 1 year), and children (younger than 5 years) worldwide and by income region. We searched several databases for articles published from Jan 1, 2000, to June 3, 2020, for publications that reported invasive GAS outcomes, and we sought unpublished data from an investigator group of collaborators. We included studies with data on invasive GAS cases, defined as laboratory isolation of Streptococcus pyogenes from any normally sterile site, or isolation of S pyogenes from a non-sterile site in a patient with necrotising fasciitis or streptococcal toxic shock syndrome. For inclusion in pooled incidence estimates, studies had to report a population denominator, and for inclusion in pooled estimates of case fatality risk, studies had to report aggregate data on the outcome of interest and the total number of cases included as a denominator. We excluded studies focusing on groups at very high risk (eg, only preterm infants). We assessed heterogeneity with I 2 ., Findings: Of the 950 published articles and 29 unpublished datasets identified, 20 studies (seven unpublished; 3829 cases of invasive GAS) from 12 countries provided sufficient data to be included in pooled estimates of outcomes. We did not identify studies reporting invasive GAS incidence among pregnant women in low-income and middle-income countries (LMICs) nor any reporting neurodevelopmental impairment after invasive GAS in LMICs. In nine studies from high-income countries (HICs) that reported invasive GAS in pregnancy and the post-partum period, invasive GAS incidence was 0·12 per 1000 livebirths (95% CI 0·11 to 0·14; I 2 =100%). Invasive GAS incidence was 0·04 per 1000 livebirths (0·03 to 0·05; I 2 =100%; 11 studies) for neonates, 0·13 per 1000 livebirths (0·10 to 0·16; I 2 =100%; ten studies) for infants, and 0·09 per 1000 person-years (95% CI 0·07 to 0·10; I 2 =100%; nine studies) for children worldwide; 0·12 per 1000 livebirths (95% CI 0·00 to 0·24; I 2 =100%; three studies) in neonates, 0·33 per 1000 livebirths (-0·22 to 0·88; I 2 =100%; two studies) in infants, and 0·22 per 1000 person-years (0·13 to 0·31; I 2 =100%; two studies) in children in LMICs; and 0·02 per 1000 livebirths (0·00 to 0·03; I 2 =100%; eight studies) in neonates, 0·08 per 1000 livebirths (0·05 to 0·11; I 2 =100%; eight studies) in infants, and 0·05 per 1000 person-years (0·03 to 0·06; I 2 =100%; seven studies) in children for HICs. Case fatality risks were high, particularly among neonates in LMICs (61% [95% CI 33 to 89]; I 2 =54%; two studies)., Interpretation: We found a substantial burden of invasive GAS among young children. In LMICs, little data were available for neonates and children and no data were available for pregnant women. Incidences of invasive GAS are likely to be underestimates, particularly in LMICs, due to low GAS surveillance. It is essential to improve available data to inform development of prevention and management strategies for invasive GAS., Funding: Wellcome Trust., Competing Interests: Declaration of interests We declare no competing interests., (Crown Copyright © 2022 Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

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.)

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites ( N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites ( N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.

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.)

On March 9, 2019, a one-day workshop titled "The current epidemiology of invasive Haemophilus influenzae disease in the Americas", jointly organized by the Public Health Agency of Canada (PHAC), the Canadian Institute of Health Research (CIHR), and the National Research Council Canada (NRC), brought together experts in the epidemiology and surveillance of invasive Haemophilus influenzae (Hi) disease from the Pan American Health Organization (PAHO) and its five regional reference laboratories in South America, USA, and Canada in Ottawa, Ontario, Canada. This workshop built upon recommendations of previous related workshops and incorporated updated data., (Copyright © 2020.)

Introduction: American Indian and Alaska Native (AI/AN) populations have higher gastric cancer rates than the general US population. This study provides a comprehensive overview of incidence rates among AI/AN persons during 2005-2016 compared with non-Hispanic whites (whites)., Methods: Population-based cancer registry data for 2005-2016 were linked with the Indian Health Service patient registration databases to address racial misclassification. Age-adjusted gastric cancer incidence rates were expressed per 100,000 per year. Incidence and trend analyses were restricted to purchased/referred care delivery area counties in 6 geographic regions, comparing gastric cancer incidence rates for AI/AN vs white populations in the United States., Results: Gastric cancer rates were higher in the AI/AN compared with white populations in nearly every US region. Incidence rates for central/distal portions of the stomach were higher in AI/AN individuals compared with whites. Rates of later stage gastric cancer were higher in AI/AN populations overall and in every region except the Pacific Coast and East. Incidence rates decreased significantly over time in both populations. Declining rates in the AI/AN populations were driven by changes in the Pacific Coast and Northern Plains regions., Discussion: AI/AN populations have a disproportionately high incidence of gastric cancer, especially in Alaska. High incidence in the central/distal portions of the stomach among AI/AN populations likely reflects a high prevalence of Helicobacter pylori infection in these populations. These data can be used to develop interventions to reduce risk factors and improve access to health services among AI/AN people at high risk for gastric cancer.

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.

Recent reports have found a rise in Hepatitis C virus (HCV) infection in reproductive age women in the USA. Surveillance data suggests one group that is at increased risk of HCV infection is the American Indian and Alaska Native population (AI/AN). Using the National Center for Health Statistics (NCHS) birth certificate and the Indian Health Services, Tribal, and Urban Indian (IHS) databases, we evaluated reported cases of HCV infection in pregnant women between 2003 and 2015. In the NCHS database, 38 regions consistently reported HCV infection. The percentage of mothers who were known to have HCV infection increased between 2011 and 2015 in both the AI/AN population (0.57% to 1.19%, p < 0.001) and the non-AI/AN population (0.21% to 0.36%, p < 0.001). The IHS database confirmed these results. Individuals with hepatitis B infection or intravenous drug use (IDU) had significantly higher odds of HCV infection (OR 16.4 and 17.6, respectively). In total, 62% of HCV-positive women did not have IDU recorded. This study demonstrates a significant increase in the proportion of pregnant women infected with HCV between 2003 and 2015. This increase was greater in AI/AN women than non-AI/AN women. This highlights the need for HCV screening and prevention in pregnant AI/AN women.

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.

Setting: The northern circumpolar jurisdictions Canada (Northwest Territories, Nunavik, Nunavut, Yukon), Finland, Greenland, Norway, Russian Federation (Arkhangelsk), Sweden and the United States (Alaska)., Objective: To describe and compare demographic, clinical and laboratory characteristics, including drug resistance and treatment completion, of tuberculosis (TB) cases in the northern circumpolar populations., Design: Descriptive analysis of all active TB cases reported from 2006 to 2012 for incidence rate (IR), age and sex distribution, sputum smear and diagnostic site characteristics, drug resistance and treatment completion rates., Results: The annual IR of TB disease ranged from a low of 4.3 per 100 000 population in Northern Sweden to a high of 199.5/100 000 in Nunavik, QC, Canada. For all jurisdictions, IR was higher for males than for females. Yukon had the highest proportion of new cases compared with retreatment cases (96.6%). Alaska reported the highest percentage of laboratory-confirmed cases (87.4%). Smear-positive pulmonary cases ranged from 25.8% to 65.2%. Multidrug-resistant cases ranged from 0% (Northern Canada) to 46.3% (Arkhangelsk). Treatment outcome data, available up to 2011, demonstrated >80% treatment completion for four of the 10 jurisdictions., Conclusion: TB remains a serious public health issue in the circumpolar regions. Surveillance data contribute toward a better understanding and improved control of TB in the north.

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.

Background: The pneumococcal conjugate vaccine (PCV) was introduced in 2001. Widespread PCV use nearly eradicated pneumococcal colonization by vaccine serotypes. Since 2008, however, colonization by PCV-serotype 19F has increased in Alaska residents. We describe the epidemiology of re-emerging serotype 19F colonization., Methods: We conducted annual cross-sectional colonization surveys from 2008 to 2013. We recruited children aged <5 years at 2 urban clinics and participants of all ages from Region-A (2 villages), Region-B (4 villages), and Region-C (2 villages). We interviewed participants and reviewed their medical records to obtain demographic information and determine PCV status. We obtained nasopharyngeal swab specimens from participants to identify pneumococci and to determine the pneumococcal serotype, antimicrobial resistance, and multilocus sequence type. We used the Cochran-Armitage test to assess for significant trends in colonization across time periods., Results: Among participants aged <5 years, pneumococcal serotype 19F colonization remained unchanged from 2008-2009 (0.7%) to 2012-2013 (0.5%; P-value [P] = .54). Serotype 19F colonization increased from 2008-2009 to 2012-2013 among participants aged 5-11 years (0.3% to 3.2%; P < .01), participants 12-17 years (0.0% to 2.0%; P < .01), and participants aged ≥18 years (0.1% to 0.5%; P < .01). During 2012-2013, 85 (93%) of 91 pneumococcal serotype 19F isolates were identified among participants from Region B; the majority of serotype 19F isolates belonged to an antimicrobial nonsusceptibility pattern corresponding to a novel multilocus sequence type 9074., Conclusions: PCV continues to protect against serotype 19F colonization in vaccinated children aged <5 years. The direct PCV impact on serotype 19F colonization in persons aged 5-11 years and indirect impact in persons aged ≥12 years is waning, possibly because of a newly introduced genotype in Region-B., (Published by Elsevier Ltd.)

Hepatitis A vaccine is recommended for children ≥1 year old to prevent hepatitis A virus (HAV) infection. However, the duration of vaccine-induced immunity is unknown. We evaluated a cohort of Alaska Native persons 20 years after HAV vaccination. Children aged 3-6 years had been previously randomized to receive three doses of HAV vaccine (360 ELISA units/dose) at: (i) 0,1,2 months; (ii) 0,1,6 months; and (iii) 0,1,12 months. We measured anti-HAV antibody concentrations every 2-3 years; described geometric mean concentrations (GMC) and the proportion with protective antibody (≥20 mIU mL -1 ) over time; and modelled the change in GMC using fractional polynomial regression. Of the 144 participants, after 20 years 52 (36.1%) were available for the follow-up (17, 18, 17 children in Groups A, B and C, respectively). Overall, 46 (88.5%) of 52 available participants had anti-HAV antibody concentrations ≥20 mIU mL -1 , and overall GMC was 107 mIU mL -1 . Although GMC levels were lower in Group A (60; CI 34-104) than in Group B (110; CI 68-177) or Group C (184; CI 98-345) (B vs C: P=.168; A vs B/C: P=.011), there was no difference between groups after adjusting for peak antibody levels post-vaccination (P=.579). Models predicted geometric mean concentrations of 124 mIU mL -1 after 25 years, and 106 mIU mL -1 after 30 years. HAV vaccine provides protective antibody levels 20 years after childhood vaccination. Lower antibody levels in Group A may be explained by a lower initial peak response. Our results suggest a booster vaccine dose is unnecessary for at least 25-30 years., (© 2017 John Wiley & Sons Ltd.)

Since the late 1990s there has been an emergence of Haemophilus influenzae serotype a (Hia) infections, especially in Indigenous communities in the northern regions of Canada and Alaska associated with significant morbidity and approximately a 10% mortality. A Hia vaccine could potentially prevent this disease and save the health care system millions of dollars in both acute and long-term care. On March 23-24, 2016, the National Research Council (NRC), the Public Health Agency of Canada (PHAC) and the Canadian Institutes of Health Research (CIHR) co-organized a meeting on H. influenzae serotype a (Hia) to examine the current state of disease epidemiology and a potential vaccine solution path. The meeting included representatives from academia, federal and territorial public health units, hospital laboratories, federal departments involved in Aboriginal health, advocacy organizations for Indigenous peoples and industry. Representatives from industry confirmed having the capacity and the interest to support preparation of clinical trial batches. Canadian regulatory authorities have expressed a willingness to help ensure appropriate measures are in place for licensure purposes. Furthermore, there is the capacity and interest in performing some clinical trials in Indigenous communities in both Canada and Alaska. Recommendations for next steps included: complete pre-clinical studies, improve epidemiological surveillance to better understand the extent of the disease in the rest of North America and globally, establish engagement mechanisms with national Indigenous organizations to ensure their peoples are fully involved in the process and explore funding opportunities to prepare clinical lots and undertake clinical trials., Competing Interests: Conflict of interest: ADC, MGB, and RSWT have no conflicts of interest to declare. MU holds an Investigator Initiated Research Grant from Pfizer for an unrelated study. LB is a Senior Scientific Advisor with Inventprise/InventVac, Redmond, Washington/Vancouver, British Columbia and a Strategic Advisor to NEOMED-LABS, Montreal, Quebec; and he has worked with the NRC Vaccine and Immune Therapeutics Group (HHT) from 2011—2015 and as a consultant for NRC in relation to Hia vaccine development. He worked with Sanofi Pasteur from 1988 to 2010 on Hib and combination vaccine development.

Background & Aims: Alaska Native people have an increased rate of hepatocellular carcinoma compared to the United States population. Viral hepatitis is a risk factor for malignancy and the leading cause of hepatocellular carcinoma in Alaska. With the introduction of hepatitis B immunization in 1982, as well as the emergence of hepatitis C virus in this population, the epidemiology and aetiology of hepatocellular carcinoma in Alaska have changed., Methods: Using the Alaska Native Tumor Registry, all cases of viral and non-viral hepatocellular carcinoma occurring from 1969 through 2013 were identified and reviewed. Incidence rates per 100 000 population were calculated for hepatocellular carcinoma overall and by aetiological category., Results: One hundred and fifty-two cases of hepatocellular carcinoma were identified in 148 Alaska Native persons. Overall tumour rate was 3.82 per 100 000 and did not change significantly over the study period. Hepatitis B-associated cases decreased significantly over the study period (P = 0.048) and were eliminated in persons under the age of 20. Hepatitis C-associated cases increased significantly (P < 0.001). Undetermined hepatocellular carcinoma rates also decreased (P = 0.034)., Conclusions: Overall hepatocellular carcinoma rates in Alaska Native people remained stable over the study period, but the epidemiology and aetiology are changing. Two decades after routine hepatitis B immunization, the hepatocellular carcinoma age distribution has shifted to cases presenting later in life. This is consistent with an ageing hepatitis B-infected population with no new infected young persons' coming into the population, as well as the emergence of hepatitis C in adults., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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 & Aims: Most regions of the world have ≤3 co-circulating hepatitis B virus (HBV) genotypes, which limits direct comparisons of hepatocellular carcinoma (HCC) risk among HBV-infected persons by genotype. We evaluated HCC incidence by HBV genotype in a cohort of Alaska Native (AN) persons where five HBV genotypes (A, B, C, D, F) have been identified., Methods: Our cohort comprised AN persons with chronic HBV infection identified during 1983-2012 who consented to participate in this study. Cohort persons were offered annual hepatitis B e antigen (HBeAg) testing and semi-annual HCC screening. We developed a logistic regression model to compare HCC risk by genotype, adjusting for age, sex, region and HBeAg status., Results: Among the 1235 consenting study participants, 711 (57.6%) were male, 510 (41.3%) were HBeAg positive at cohort entry and 43 (3.5%) developed HCC. The HBV genotype was known for 1142 (92.5%) persons (13.5% A, 3.9% B, 6.7% C, 56.9% D, 19.0% F). The HCC incidence/1000 person-years of follow-up for genotypes A, B, C, D and F was 1.3, 0, 5.5, 0.4 and 4.2 respectively. Compared with persons with HBV genotype B/D infection, the HCC risk was higher for persons with genotypes A [adjusted odds ratio (aOR): 3.9, 95% confidence interval (CI): 1.14-13.74], C (aOR: 16.3, 95% CI: 5.20-51.11) and F (aOR: 13.9, 95% CI: 5.30-36.69)., Conclusion: HBV genotype is independently associated with HCC risk. AN persons with genotypes A, C and F are at higher risk compared with genotypes B or D., Competing Interests: None of the authors have any relevant conflicts of interest to disclose., (Published 2016. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Long-lasting protection resulting from hepatitis B vaccine, despite loss of antibody against hepatitis B virus (HBV) surface antigen (anti-HBs), is undetermined., Methods: We recruited persons from a cohort vaccinated with plasma-derived hepatitis B vaccine in 1981 who have been followed periodically since. We performed serological testing for anti-HBs and microRNA-155 and assessed HBV-specific T-cell responses by enzyme-linked immunospot and cytometric bead array. Study subgroups were defined 32 years after vaccination as having an anti-HBs level of either ≥10 mIU/mL (group 1; n = 13) or <10 mIU/mL (group 2; n = 31)., Results: All 44 participants, regardless of anti-HBs level, tested positive for tumor necrosis factor α, interleukin 10, or interleukin 6 production by HBV surface antigen-specific T cells. The frequency of natural killer T cells correlated with the level of anti-HBs (P = .008). The proportion of participants who demonstrated T-cell responses to HBV core antigen varied among the cytokines measured, suggesting some natural exposure to HBV in the study group. No participant had evidence of breakthrough HBV infection., Conclusions: Evidence of long-lasting cellular immunity, regardless of anti-HBs level, suggests that protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 32 years., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)