BACKGROUND:Vaccination is effective at preventing chronic HBV infection and its complications, but the duration of protection and need for booster doses have not been determined. METHODS:We administered a 3-dose primary series of plasma-derived hepatitis B vaccine to Alaska Native persons aged 6 months or above who resided in an HBV-endemic area of western Alaska. Persons with antibody to hepatitis B surface antigen (anti-HBs) ≥10 milli-international units per milliliter (mIU/mL) at 6 months after series completion were followed through 41 years after vaccination. Beginning at 22 years, participants with anti-HBs <10 mIU/mL were offered a booster dose (ie, challenge dose) of recombinant hepatitis B vaccine and retested 4 weeks later as a surrogate for immune memory. Combining these immune-memory data with a survival model estimating anti-HBs persistence, we estimated the overall proportion with serologic evidence of protection at 22, 30, 35, and 41 years. We also described breakthrough hepatitis B infections. RESULTS:During 1981-1982, 1351 persons completed the hepatitis B vaccine primary series and had anti-HBs ≥10 mIU/mL at 6 months after vaccination; median age at enrollment was 13 years (range: 0.5-77). The overall proportion with serologic evidence of protection was 95% at 22 years, 95% at 30 years, 88% at 35 years, and 91% at 41 years after vaccination. At 41 years, 32% had circulating anti-HBs ≥10 mIU/mL, and 59% had immune memory. During 41 years of follow-up, 16 (1%) persons had evidence of a breakthrough infection; none developed chronic hepatitis B. CONCLUSIONS:We found serologic evidence of protection among Alaska Native persons 41 years after primary hepatitis B vaccination. Our findings support the recommendation that booster doses are not needed in endemic areas.

Human papillomavirus (HPV)-associated cancers are vaccine preventable. In 2016, the previously recommended three-dose HPV vaccination series was changed to a two-dose series and nine-valent HPV vaccine (9vHPV) became the only HPV vaccine available in the United States. Data on longer-term duration of antibodies following a 9vHPV two-dose series are limited. We evaluated the immunogenicity and duration of antibodies up to three years after vaccination with a two-dose series of 9vHPV in a cohort of Alaska Native children. We enrolled Alaska Native children aged 9–14 years who received 9vHPV in Anchorage, Alaska during 2017–2018. We collected sera at six months after dose one and at one month, one year, and three years after dose two to measure type-specific immunoglobulin G (IgG) concentrations for the 9vHPV types (HPV6/11/16/18/31/33/45/52/58). Aggregate type-specific IgG concentrations were reported as geometric mean concentrations (GMC). A total of 227 children completed the two-dose series of 9vHPV and provided ≥ 1 blood sample. The median age at enrollment was 11.0 years (range: 9.0–14.6) and was similar between males and females (p = 0.11). At one month after dose two, all 197 participants with available serum were seropositive for all 9vHPV types. Among 145 participants who had a specimen available at three years after dose two, 134 (92

Objectives:In the US, hepatitis B virus (HBV) is only endemic in western Alaska, where 90% of the population are Alaska Native (AN) peoples; in the 1970s, the incidence of hepatocellular carcinoma (HCC) in children was the highest in the world. In the 1980s, we screened 53,860 AN peoples for HBV infection, administered HBV vaccine to 43,618 HBV seronegative persons, and initiated universal newborn vaccination. In this study, we examine the impact of this effort 40 years later. Methods:This is a population-based outcome study. We used vaccine and electronic health records to examine rates of newborn vaccination between 2015 and 2019 and changes in HBV incidence rates, as well as the prevalence of HCC in persons under 30 years of age over a 50-year period. Results:Between 2015 and 2019, approximately 90% of newborns received an HBV birth dose, and over 80% received a second HBV vaccine dose by 18 months of age. Annual incidence of new hepatitis B surface antigen-positive tests among AN peoples ranged from 1.4-2.6 per 100,000, down from 6.2 between 1993 and 1997. No hepatitis B surface antigen-positive or HCC cases have been identified in AN peoples under 20 since 1993. Conclusions:Mass population-based vaccination of seronegative persons, with continuing universal newborn immunization, halted transmission of HBV in western Alaska.

OBJECTIVE:Potentially preventable hospitalizations are inpatient admissions for a standard set of selected acute illnesses and chronic conditions that might have been avoided with preventive care or outpatient management. During 2010-2012, Alaska Native adults had higher rates of potentially preventable hospitalizations compared to other adults in Alaska. We evaluated potentially preventable hospitalizations among American Indian/Alaska Native (AI/AN) adults in the United States during 2016-2021. METHODS:We used hospital discharge data from the Indian Health Service National Patient Information Reporting System (NPIRS) to calculate and compare average annual age-adjusted rates of potentially preventable hospitalizations per 1000 AI/AN adults for two acute conditions (community-acquired pneumonia and urinary tract infection) and four chronic conditions (diabetes, heart failure, asthma/chronic obstructive pulmonary disease, and hypertension). RESULTS:Of 310,889 hospitalizations among AI/AN adults, 40,400 (13 %) were defined as potentially preventable for an annual rate of 7.6 per 1000 persons. Rates were stable during 2016-2019 (8.7 per 1000) but declined during 2020-2021 (5.9 per 1000), likely related to the COVID-19 pandemic. Older adults and rural residents had significantly higher rates of potentially preventable hospitalizations across all six conditions assessed, with community-acquired pneumonia having the highest hospitalization rate among adults aged ≥65 years (5.2 per 1000). CONCLUSIONS:Targeted preventive care and appropriate outpatient management for AI/AN elders living in rural areas might help improve health and reduce medical costs through decreased hospitalizations. Vaccination against respiratory infections could have the greatest impact in reducing preventable hospitalizations among AI/AN adults.

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 U.S. adults. We described the epidemiology of IPD among Alaska adults and estimated 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 (CI) 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, 1,164 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<0.01). 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 the general adult population (95% CI: 59-89). Overall, 1,032 (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.

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.

ABSTRACT 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.

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 postvaccination. 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.

The Arctic and Antarctic regions are characterized by sparse populations living in small, isolated settlements which tend to have crowded households. Although there are regional differences, living conditions and disease patterns for these populations are relatively comparable. Scientific studies on infectious diseases in Arctic regions inhabited by indigenous people are most often performed on high-incident diseases. A number of infectious diseases such as invasive disease caused by Streptococcus pneumoniae and Haemophilus influenzae, tuberculosis, chronic otitis media, hepatitis B virus, sexually transmitted infections, Helicobacter pylori, parasitic infections, and bacterial zoonoses occur at higher rates in Arctic regions than in their southern counterparts. This chapter describes infections with known high prevalence in the Arctic regions of Alaska, Canada, Greenland, and Siberia. The infectious disease patterns for persons living in and traveling to Svalbard and the Antarctic reflect those of their corresponding populations (e.g. Norway for Svalbard and countries of origin for persons traveling to the Antarctic).

We evaluated factors associated with the presence of hepatitis A virus antibodies 23 years after initiating vaccination at ages 6-15 months. Among 67 participants, 86% (42/49) of those vaccinated at ages 12-15 months and 61% (11/18) of those vaccinated at 6 months remained seropositive at 23 years. Lack of maternal antibodies at enrollment and higher initial vaccine response were independently associated with higher antibody concentrations at 23 years. Further research is needed to assess the duration of hepatitis A vaccine protection and possible need for a booster dose.

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

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.

BACKROUND AIMS A functional cure and therapeutic endpoint of chronic hepatitis B virus (HBV) infection is defined as clearance of hepatitis B surface antigen (HBsAg) from serum. Little is known about the long-term durability of HBsAg loss in the Alaskan Native population. APPROACH RESULTS We performed a retrospective cohort study of Alaskan Native patients with chronic HBV-monoinfection from January, 1982 through December 2019. The original group in this cohort were identified during a 1982 to 1987 population-based screening for three 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 afterwards to assess durability of HBsAg clearance. Among 1,079 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 260 persons who cleared, 249 (96%) remained HBsAg negative while 11 persons had≥ 2 transient HBsAg positive results in subsequent follow-up. CONCLUSIONS Of patients with chronic HBV monoinfection, 0.82% of people per year achieved a functional cure. HBsAg seroclearance was durable for treated and non-treated patients and lasted on average over 13 years without seroreversion. The findings and conclusions in this report are those of the authors and do not necessarily represent the official positions of the Centers for Disease Control and Prevention.

Background: Studies report increased risk of incident diabetes following COVID-19 illness. American Indian/Alaska Native (AI/AN) people have had more frequent and severe COVID-19 illness and historically higher diabetes incidence than other racial/ethnic groups in the US. We examined the association between COVID-19 illness and incident diabetes in AI/AN people. Methods: Using de-identified data from the Indian Health Service, we created three cohorts spanning two periods: COVID-19 cohort and no-COVID-19 cohort (no indication of COVID-19 infection) both from 3/1/2020-12/31/2021 and pre-COVID-19 cohort from 1/1/2018-2/28/2020. We used data from the year prior to cohort entry to exclude prevalent cases of diagnosed diabetes (diagnosis codes, labs, or diabetes medications) and assess baseline characteristics. During the study period we ascertained COVID-19 infection (diagnosis codes, labs) and incident diabetes. We calculated age-adjusted diabetes incidence rates and rate ratios comparing the COVID-19 cohort to the no-COVID-19 and pre-COVID-19 cohorts. Results: Across cohorts, age, sex, and healthcare utilization differed. Age-adjusted diabetes incidence rates and rate ratios were significantly higher in the COVID-19 cohort (Table 1). Conclusions: Clinically confirmed COVID-19 infection was associated with increased incident diabetes rates in AI/AN people. Disclosure J.Keck: None. S.Bressler: None. M.Bruce: None. U.Chukwuma: None. M.E.Lacy: None. Funding National Institutes of Health (R34DK132548-01S1)

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.

Background Haemophilus influenzae serotype a (Hia) can cause severe invasive disease, especially in young children. In 2018, 4 invasive Hia cases occurred in an Alaska community. We used whole-genome sequencing (WGS) to evaluate the relationship of the bacteria from this community and other Alaska patients with invasive Hia. Methods All carriage (n = 15) and invasive (n = 4) Hia isolates from the outbreak community, together with 15 nonoutbreak Alaska invasive Hia surveillance isolates from 2018, were tested for antimicrobial susceptibility and characterized using WGS. Results Phylogenetic analysis of both invasive and carriage Hia isolates revealed 2 major clades that differed by an average of 300 core single-nucleotide polymorphisms (SNPs). All isolates from the outbreak community were clustered in 1 subclade, within a larger clade containing 3 nonoutbreak invasive Hia isolates. Comparative genomics did not reveal any genetic mutations that distinguished carriage from invasive isolates. Three (20%) community isolates were rifampin resistant and had a previously unreported mutation in the rpoB gene. Conclusions In the outbreak community, Hia isolates from carriers were indistinguishable from the invasive Hia isolates. Overall, invasive Hia isolates from Alaska in 2018 were genetically similar. The rifampin resistance mutation is concerning as rifampin is the first-line medication for Hia prophylaxis.

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.

Isolation is recommended during acute infection with SARS-CoV-2, the virus that causes COVID-19, but the duration of infectiousness varies among individual persons. Rapid antigen test results have been correlated with detection of viable virus (1-3) and might inform isolation guidance, but data are limited for the recently emerged SARS-CoV-2 B.1.1.529 (Omicron) variant. On January 5, 2022, the Yukon-Kuskokwim Health Corporation (YKHC) recommended that persons with SARS-CoV-2 infection isolate for 10 days after symptom onset (or, for asymptomatic persons, 10 days after a positive nucleic acid amplification or antigen test result). However, isolation could end after 5-9 days if symptoms were resolving or absent, fever was absent for ≥24 hours without fever-reducing medications, and an Abbott BinaxNOW COVID-19 Ag (BinaxNOW) rapid antigen test result was negative. Antigen test results and associated individual characteristics were analyzed among 3,502 infections reported to YKHC during January 1-February 9, 2022. After 5-9 days, 396 of 729 persons evaluated (54.3%) had a positive antigen test result, with a declining percentage positive over time. In a multivariable model, a positive antigen test result was more likely after 5 days compared with 9 days (adjusted odds ratio [aOR] = 6.39) or after symptomatic infection (aOR = 9.63), and less likely after previous infection (aOR = 0.30), receipt of a primary COVID-19 vaccination series (aOR = 0.60), or after both previous infection and receipt of a primary COVID-19 vaccination series (aOR = 0.17). Antigen tests might be a useful tool to guide recommendations for isolation after SARS-CoV-2 infection. During the 10 days after infection, persons might be infectious to others and are recommended to wear a well-fitting mask when around others, even if ending isolation after 5 days.

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.