BACKGROUND: 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. METHODS: 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). RESULTS: 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%) remained seropositive for all 9vHPV types. GMC peaked for all types at one month post dose two and remained higher at three years post dose two compared to six months post dose one. CONCLUSIONS: We found high immunogenicity and antibody persistence after a two-dose series of 9vHPV in this cohort of Alaska Native children. Further follow-up will determine duration of antibody detection in this cohort.

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: Pneumococcal conjugate vaccines (PCVs) introduced in childhood national immunization programs lowered vaccine-type invasive pneumococcal disease (IPD), but replacement with non-vaccine-types persisted throughout the PCV10/13 follow-up period. We assessed PCV10/13 impact on pneumococcal meningitis incidence globally. METHODS: The number of cases with serotyped pneumococci detected in cerebrospinal fluid and population denominators were obtained from surveillance sites globally. Site-specific meningitis incidence rate ratios (IRRs) comparing pre-PCV incidence to each year post-PCV10/13 were estimated by age (<5, 5-17 and ≥18 years) using Bayesian multi-level mixed effects Poisson regression, accounting for pre-PCV trends. All-site weighted average IRRs were estimated using linear mixed-effects regression stratified by age, product (PCV10 or PCV13) and prior PCV7 impact (none, moderate, or substantial). Changes in pneumococcal meningitis incidence were estimated overall and for product-specific vaccine-types and non-PCV13-types. RESULTS: Analyses included 10,168 cases <5 y from PCV13 sites and 2849 from PCV10 sites, 3711 and 1549 for 5-17 y and 29,187 and 5653 for ≥18 y from 42 surveillance sites (30 PCV13, 12 PCV10, 2 PCV10/13) in 30 countries, primarily high-income (84%). Six years after PCV10/PCV13 introduction, pneumococcal meningitis declined 48-74% across products and PCV7 impact strata for children <5 y, 35-62% for 5-17 y and 0-36% for ≥18 y. Impact against PCV10-types at PCV10 sites, and PCV13-types at PCV13 sites was high for all age groups (<5 y: 96-100%; 5-17 y: 77-85%; ≥18 y: 73-85%). After switching from PCV7 to PCV10/13, increases in non-PCV13-types were generally low to none for all age groups. CONCLUSION: Pneumococcal meningitis declined in all age groups following PCV10/PCV13 introduction. Plateaus in non-PCV13-type meningitis suggest less replacement than for all IPD. Data from meningitis belt and high-burden settings were limited.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages. METHODS: Serotype-specific IPD cases and population denominators were obtained directly from surveillance sites using PCV10 or PCV13 in their national immunisation programmes and with a primary series uptake of at least 50%. Annual incidence rate ratios (IRRs) were estimated comparing the incidence before any PCV with each year post-PCV10 or post-PCV13 introduction using Bayesian multi-level, mixed-effects Poisson regressions, by site and age group. All site-weighted average IRRs were estimated using linear mixed-effects regression, stratified by product and previous seven-valent PCV (PCV7) effect (none, moderate, or substantial). FINDINGS: Analyses included 32 PCV13 sites (488 758 cases) and 15 PCV10 sites (46 386 cases) in 30 countries, primarily high income (39 sites), using booster dose schedules (41 sites). By 6 years after PCV10 or PCV13 introduction, IPD due to PCV10-type serotypes and PCV10-related serotype 6A declined substantially for both products (age <5 years: 83-99% decline; ≥65 years: 54-96% decline). PCV7-related serotype 19A increases before PCV10 or PCV13 introduction were reversed at PCV13 sites (age <5 years: 61-79% decline relative to before any PCV; age ≥65 years: 7-26% decline) but increased at PCV10 sites (age <5 years: 1·6-2·3-fold; age ≥65 years: 3·6-4·9-fold). Serotype 3 IRRs had no consistent trends for either product or age group. Non-PCV13-type IPD increased similarly for both products (age <5 years: 2·3-3·3-fold; age ≥65 years: 1·7-2·3-fold). Despite different serotype 19A trends, all-serotype IPD declined similarly between products among children younger than 5 years (58-74%); among adults aged 65 years or older, declines were greater at PCV13 (25-29%) than PCV10 (4-14%) sites, but other differences between sites precluded attribution to product. INTERPRETATION: Long-term use of PCV10 or PCV13 reduced IPD substantially in young children and more moderately in older ages. Non-vaccine-type serotypes increased approximately two-fold to three-fold by 6 years after introduction of PCV10 or PCV13. Continuing serotype 19A increases at PCV10 sites and declines at PCV13 sites suggest that PCV13 use would further reduce IPD at PCV10 sites. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

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.

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 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.

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.

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.

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.

We read with interest the editorial by Lee et al1 | that highlighted | the challenge of elevated rates of H pylori‐associated gastric can‐ | cer among Alaska Native people and recognized our ongoing work | in Alaska to document and address this health disparity. As health | practitioners in Alaska, we share their concerns about the elevated | gastric cancer rates and would welcome increased efforts to reduce | the health threats associated with H pylori infection; however, some | of their points require a response. The authors posit that H pylori | eradication programs and pilot studies used in Japan and Taiwan | should be applied to Alaska. While such studies offer an intriguing | approach, early results have not completely answered the question | of how to prevent gastric cancer. The absence of evidence‐based | guidelines and the lack of national or professional society recom‐ | mendations supporting population‐level H pylori eradication are a | strong indication that this approach is not yet proven. There are im‐ | portant unanswered questions about the risks and benefits of such | an eradication program. These risks include, but are not limited to, | the potential to develop worsening antimicrobial resistance among | H pylori and antimicrobial resistance among non‐targeted commen‐ | sal or pathogenic organisms, and the risk of causing harm by giving | antibiotics to healthy persons who may not be at risk for gastric can‐ | cer (eg, allergic responses, drug‐drug interactions, Clostridium diffi‐ | cile infections). Additional unanswered questions relevant for Alaska | include the effectiveness and feasibility of a population‐level H pylori | eradication program in a remote population with high rates of H py‐ | lori reinfection, a high proportion of H pylori isolates demonstrating | antimicrobial resistance, and documented high rates of treatment | failure. Even if the health benefit of a population‐based eradication | effort were to be established, concerns about funding, logistical op‐ | erations, and the relative value of such a program compared with | other high priority health concerns would need to be considered. In | Alaska, such concerns are magnified, where our ~200 rural commu‐ | nities are dispersed over a mostly roadless area larger than Texas, | Taiwan, and Japan combined

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: 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.

BACKGROUND: 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 or older. METHODS: We tested persons for anti-HBs levels 35 years after receiving the primary series. Those with levels <10 mIU/ml received 1 booster dose of recombinant hepatitis B vaccine 2-4 weeks later and were then evaluated on the basis of anti-HBs measurements 30 days post-booster. RESULTS: Among the 320 recruited, 112 persons had not participated in the 22 nor 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% (28/38) 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 anti-HBc, none tested positive for HBsAg nor HBV DNA. CONCLUSIONS: Based on anti-HBs level ≥10 mIU/ml at 35 years and a 73.7% booster dose response, we estimate 86% of participants had evidence of protection 35 years later. Booster doses are not needed in the general population at this time.

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.

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.

OBJECTIVES: In this study, we describe changes in LRTI rates from 1998-2014 among hospitalized AI/AN adults residing in Alaska and other Indian Health Service (IHS) regions. METHODS: We calculated age-adjusted hospital discharge rates and rate ratios 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 13.7/1,000 adults. Among non-AK AI/AN, there were a total of 79,170 hospitalizations with a rate of 8.6/1,000 adults. In the pre-PCV7 and pre-PCV13 periods, LRTI rates were higher in AK AI/AN (12.4 and 14.1) compared to non-AK AI/AN (10.1 and 9.1, p<0.0001), respectively. In post-PCV7 and post-PCV13 periods, LRTI rates were also higher in AK (13.5 and 15.0) compared to non-AK (9.2 and 7.3, p<0.0001). CONCLUSIONS: Over the study period, we observed a 26% increase in rates of LRTI among adult AI/AN residing in Alaska compared with a 38% decrease in rates among AI/AN residing in non-AK. 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.

Boils are a major health problem affecting rural Alaska Native communities. Boils result from transmission of Staphylococcus aureus from steam bath surfaces, infected skin, and household environments. To assess the acceptability of practices to prevent boils within one community, we surveyed 57 households before and after distribution of supplies and educational materials. Before distribution, 64% of households cleaned steam baths with bleach (23/36), 72% used steam bath seat barriers (41/57), 74% did not share scrubbers (42/57), 35% added recommended bleach to laundry (20/57), and 30% used hand sanitizer (17/57). After distribution, 75% households used new scrubbers (43/57), 88% used new seat barriers (50/57), and 25% used new antiseptic skin cleanser (14/57). Additionally, after the intervention, more households used seat barriers in steam baths (from 72% to 86%, p = .046) and hand sanitizer (from 30% to 60%, p < .001). This study supports development of a household-based intervention as a potential strategy to prevent boils in Alaska Native communities.

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: Stomach cancer incidence and mortality rates are declining across circumpolar nations, but the burden may not be distributed equally across sub-populations, 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 ten-year rolling age-standardized incidence and mortality rates to the World (WHO 2000-2025) and 2011 Canadian standard populations. Standardized incidence rate ratios (SRRs) were calculated. Data were stratified by sex, year and region. US data were broken down by race (White; American Indian/Alaska Native (AIAN)). Race data were not available from non-US 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 to regional counterparts and remained stable. The largest male SRR was observed among Alaska AIAN versus Alaska Whites (SRR=3.82, 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 sub-populations. Given similarities in incidence, mortality and risk factor prevalence across circumpolar regions, addressing disparities could benefit from coordinated international action.

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.

With great interest, we read the article by Thrift and El-Serag1 providing an overview of the epidemiology, risk factors, prevention, and surveillance approaches to gastric cancer. The article highlights one of the most prevalent and under-recognized malignances throughout the world, and we appreciate the authors’ discussion of this topic. Although they nicely describe varying incidence rates by geography and race/ethnicity in the United States, they failed to describe the population with the highest incidence rate in the United States, Alaska Native (AN) people.

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.

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.

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.

BACKGROUND: Haemophilus influenzae bacteria can cause asymptomatic carriage and invasive disease. H. 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 IgG antibodies against Hia (anti-Hia) in 839 banked serum samples from Alaska residents, comparing antibody concentrations in samples drawn in the decades prior to (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: Anti-Hia was >0.1 microg/mL in 88.1% (348/395) and 91.0% (404/444) of samples from the decades prior and after the emergence of Hia, respectively (p=0.17). No significant differences in antibody levels were detected between people from rural and urban regions (1.55 microg/mL vs. 2.08 microg/mL, p=0.91 for age >/=5) or between AN and non-AN people (2.50 microg/mL vs 2.60 microg/mL, p=0.26). 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.

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 2008-2017, 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, incidence was 17 times higher among American Indians 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 U.S. 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.

BACKGROUND: Between May and July 2018, four invasive Haemophilus influenzae serotype a (iHia) infections occurred in a remote Alaska community. We performed a public health response to prevent further illness and understand Hia carriage in the community. METHODS: We collected oropharyngeal (OP) samples community-wide from untreated individuals to evaluate baseline carriage. Risk factor data was collected by interview. To prevent additional illness, we offered prophylactic rifampin to individuals in contact with iHia patients (contacts) and to all children aged <10 years. OP samples were collected again eight weeks post-rifampin distribution. Samples were tested using real-time PCR and culture. RESULTS: At baseline, Hia was carried by 4/27 (14.8%) contacts and 7/364 (1.9%) non-contacts (p<0.01). Contacts aged <10 years were more likely to carry Hia at any timepoint (11/18, 61%) than contacts aged >/=10 years (3/34, 8.8%) or non-contacts aged <10 years (2/139, 1.4%) and >/=10 years (6/276, 2.2%)(p<0.001 for all). Hia carriers were clustered in nine households (7% of total households). At the household level, carriage was associated with households with >/=1 contact (PR=5.6, CI:1.3-21.6), crowding (PR=7.7, CI:1.1-199.5) and >/=3 tobacco users (PR=5.0, CI:1.2-19.6). Sixty-six percent (40/61) of contacts and 90% (111/124) of non-contacts aged <10 years received rifampin. Elevated carriage prevalence persisted in contacts when retested eight weeks after rifampin distribution (contacts 6/25 (24%), non-contacts 2/114 (1.8%), p<0.001). CONCLUSIONS: Hia carriage prevalence was significantly higher among people who had contact with iHia patients than the general community. Rifampin prophylaxis did not result in a reduction of Hia carriage prevalence in this community.