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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.

Invasive

Controlling the spread of SARS-CoV-2, the virus that causes COVID-19, in Alaska is challenging. Alaska includes many remote and isolated villages with small populations (ranging from 15 to >1,000 persons) that are accessible only by air from larger communities. Until rapid point-of-care testing became widely available, a primary challenge in the diagnosis of COVID-19 in rural Alaska was slow turnaround times for SARS-CoV-2 test results, attributable to the need to transport specimens to testing facilities. To provide more timely test results and isolation of cases, the Yukon Kuskokwim Health Corporation (YKHC) introduced Abbott BinaxNOW COVID-19 Ag rapid antigen test (BinaxNOW) on November 9, 2020, in the rural Yukon-Kuskokwim Delta region in southwestern Alaska. To evaluate the impact of implementing antigen testing, YKHC reviewed the results of 54,981 antigen and molecular tests for SARS-CoV-2 performed in the Yukon-Kuskokwim Delta during September 15, 2020-March 1, 2021. Introduction of rapid, point-of-care testing was followed by a more than threefold reduction in daily SARS-CoV-2 case rates during approximately 1 month before the introduction of COVID-19 vaccination. The median turnaround time for SARS-CoV-2 test results decreased by >30%, from 6.4 days during September 15-November 8, 2020, to 4.4 days during November 9, 2020-March 1, 2021 (p

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: 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.

There exists no coherent national strategy for the early detection or prevention of gastric cancer in the United States (US), even among identified high-risk groups such as Asian Americans, African Americans, Hispanic Americans, and Alaska Native/American Indian peoples. As a result, patients with gastric cancer in the US are diagnosed at later stages and demonstrate worse overall survival compared to nations of East Asia with established screening programs (Table 1). The under-recognition of gastric cancer risk within minority communities is a significant unaddressed healthcare disparity.

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.

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.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.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.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.

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

The 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.We tested persons for antibody to hepatitis B surface antigen (anti-HBs) levels 35 years after receiving the primary series. Those with levels10 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.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.

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.

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.

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.

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.

Background: The incidence of invasive disease caused by group A Streptococcus (GAS) has recently increased in multiple countries. To inform interventions such as GAS vaccines currently in development, we estimated the incidence of invasive GAS (iGAS) disease, including death and disability outcomes, among two high risk groups—pregnant women and children under 5 years of age. Methods: We searched a range of databases and sought unpublished data to identify inputs (1 st January 2000 and 30 th June 2020) to calculate pooled incidence of iGAS disease, case fatality risks (CFRs), and neurodevelopmental impairment among pregnant women, neonates, infants, and children (under 5 years of age). Findings: We identified 950 published articles and 29 unpublished datasets for consideration. Of these 20 studies were eligible for meta-analyses; no studies among pregnant women or on neurodevelopmental impairment in low- and middle-income countries (LMICs) were available. In high income countries (HICs), iGAS incidence among pregnant women was 0·12/1000 live births (95%CI 0·11-0·14). Worldwide iGAS incidence estimates included: neonates, 0·04/1000 live births (0·03-0·05); infants, 0·13/1000 live births (0·10-0·16); and, children aged 0-5 years, 0·09/1000 person-years (95%CI 0·07-0·10). Incidences among children were higher in LMICs, particularly in neonates (0·12/1000 live births; 95%CI 0·00-0·24) compared to HICs (0·02/1000 live births; 0·00-0.03). CFRs among young children were high, particularly among neonates in LMICs (61%; 95%CI 33-89%). Interpretation: We found a high disease incidence and risk of death among young children with iGAS, particularly in LMICs. Notably, for LMICs, limited data are available for neonates and children, and no data are available for pregnant women. Incidences are likely underestimated, particularly in LMICs, due to limited GAS surveillance. Improving available data is essential to inform GAS vaccine development and evaluation. Funding: ACSe is funded by The Wellcome Trust. ACSt is funded by a Viertel Senior Medical Research Fellowship. Declaration of Interest: We declare no competing interests

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 &lt, 5 years of age and 15% among ≥5 years, the top serotypes were 19A, 6C, and 3, together causing 42% of cases &lt, 5 years and 37% ≥5 years. In PCV13-using sites (N = 32, cases = 4503), PCV13 types caused 14% in &lt, 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.

Hepatitis B virus (HBV) infection remains a global health threat. The World Health Organization (WHO) established a goal to eliminate HBV infection as a public health threat by 2030, and defined targets for key interventions to achieve that goal. We evaluated HBV burden and relevant national recommendations for progress towards WHO targets in circumpolar countries. Viral hepatitis experts of circumpolar countries were surveyed regarding their country’s burden of HBV, achievement of WHO targets and national public health authority recommendations for HBV prevention and control. Eight of nine circumpolar countries responded. All countries continue to see new HBV infections. Data about HBV prevalence and progress in reaching WHO 2030 elimination targets are lacking. No country was able to report data for all seven WHO target measures. All countries have recommendations targeting the prevention of mother-to-child transmission. Only the USA and Greenland recommend universal birth dose vaccination. Four countries have recommendations to screen persons at high risk for HBV. Existing recommendations largely address prevention; however, recommendations for universal birth dose vaccination have not been widely introduced. Opportunities remain for the development of trackable targets and national elimination planning to screen and treat for HBV to reduce incidence and mortality.

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.

The hepatitis A vaccine is recommended for all children greater than or equal to 1 year of age, however, the duration of vaccine protection is unknown and protection through adulthood is crucial to prevent symptomatic hepatitis later in life. We report on 25 years of follow-up of a cohort of Alaska Native individuals who were vaccinated in early childhood. We assessed the duration of vaccine protection by calculating the geometric mean concentration and proportion of participants with protective levels of IgG antibody to hepatitis A virus (anti-HAV) (≥20 mIU/mL) every 2 to 3 years. We estimated the amount of time until the anti-HAV dropped below protective levels using survival analyses. At 25 years, 43 of the original 144 participants were available, mean anti-HAV levels were 91.5 mIU/mL, and 35 (81.4%) had protective levels of anti-HAV. Using data from all persons and all time points, a survival analysis estimated 78.7% of participants had protective levels of anti-HAV at 25 years. The high level of protective antibodies in this cohort indicate that supplemental doses of hepatitis A vaccine are not needed 25 years after completion of the vaccine series.

To determine the duration of immunity provided by the Hepatitis A vaccination (HepA), we evaluated a cohort of participants in Alaska 20 years after being immunized as infants. At recruitment, participants received two doses of inactivated HepA vaccine on one of three schedules. We conducted hepatitis A antibody (anti-HAV) testing for participants at the 20-year time-point. Seventy-five of the original 183 participants (41%) were available for follow-up. The overall anti-HAV geometric mean concentration was 29.9 mIU/mL (95% CI 22.4 mIU/mL, 39.7 mIU/mL) and 50 participants (68%) remained seropositive (titer ≥ 20 mIU/mL). Using a fractional polynomial model, the predicted percent seropositive at 25 years was 55.3%, 49.8% at 30 years and 45.7% at 35 years, suggesting that the percent sero-positive could drop below 50% earlier than previously expected. Further research is necessary to understand if protection continues after seropositivity diminishes or if a HepA booster dose may become necessary.

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.

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 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.

Alaska Natives experience a high burden of Helicobacter pylori infection and concomitant high rates of gastric cancer. Additionally, the prevalence of antimicrobial-resistant H. pylori has been shown to be high in Alaska. In this study, antimicrobial resistance over time among sentinel surveillance isolates was evaluated and risk factors for carrying antimicrobial-resistant H. pylori were assessed.Through Alaska's H. pylori sentinel surveillance system, antral and fundal biopsies from Alaska Native patients undergoing esophagogastroduodenoscopy for clinical indications during 2000-2016 were collected and cultured. For positive cultures, minimum inhibitory concentrations (MICs) of metronidazole, amoxicillin, clarithromycin, tetracycline and levofloxacin were determined.A total of 800 H. pylori isolates obtained from 763 patients were tested. Resistance to metronidazole was most common (342/800; 42.8%), followed clarithromycin (238/800; 29.8%), both clarithromycin and metronidazole (128/800; 16.0%) and levofloxacin (113/800; 14.1%). Low proportions of isolates were resistant to amoxicillin and tetracycline. Levofloxacin resistance increased between 2000 and 2016 (P0.001), but resistance to other antimicrobials did not change over time. Metronidazole and clarithromycin resistance were more common among women (P0.001 for both), whilst levofloxacin resistance was more common among those with an urban residence (P=0.003). Metronidazole and levofloxacin resistance were more common among older patients (P0.05).Between 2000 and 2016, a large percentage of H. pylori isolates received by the Alaska Sentinel Surveillance System demonstrated resistance to common antimicrobials. The surveillance system provides valuable information for clinicians to make informed treatment choices for patient with H. pylori.

Giardia duodenalisandCryptosporidiumspp. are common intestinal protozoa that can cause diarrhoeal disease. Although cases of infection withGiardiaandCryptosporidiumhave 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 theGiardia duodenalisvariant-specific surface protein conserved structural regions and to theCryptosporidium parvum17- and 27-kDa antigens. Approximately one third of participants in each group had evidence of exposure toCryptosporidium. Prevalence ofGiardiaantibody 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 toGiardia.

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

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 (WGS) 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 six facilities in Anchorage a single dose of 1 gram of azithromycin. We collected oropharyngeal and non-intact skin swabs on a subset of participants concurrent with the intervention and 4 weeks afterward. RESULTS: From July 2016–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=0.04) and necrotizing fasciitis (OR 4.4, p=0.02). 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=0.05). 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=0.01). CONCLUSIONS: In an invasive GAS outbreak in PEH in Anchorage, mass antibiotic administration was temporally associated with reduced invasive disease cases and colonization prevalence.

Long-term prospective studies of the outcomes associated with hepatitis C virus (HCV) infection are rare and critical for assessing the potential impact of HCV treatment. Using liver biopsy as a starting point, we analyzed the development of end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), and liver-related death (LRD) according to fibrosis stage among a cohort of American Indian/Alaska Native persons in Alaska. Persons were classified as having no/mild (Ishak = 0,1), moderate (Ishak = 2), or severe (Ishak = 3,4) fibrosis or cirrhosis (Ishak = 5,6). We examined time until development of ESLD, HCC, and LRD and report survival probabilities at 3, 5, 7, and 10 years. Of 407 persons, 39% (n = 150) had no/mild fibrosis, 32% (n = 131) had moderate fibrosis, 22% (n = 88) had severe fibrosis, and 9% (n = 38) had cirrhosis. The average time of follow-up was 7.3 years. Within 5 years of biopsy, 1.7% (95% confidence interval [CI]: 0.4-6.8) of persons with no/mild fibrosis developed ESLD compared with 7.9% (95% CI, 4.0-15.2), 16.4% (95% CI, 9.6-27.2), and 49.0% (95% CI, 33.0-67.7) with moderate, severe fibrosis, and cirrhosis, respectively (P < 0.01). The 5-year outcome of HCC was 1.0% (95% CI, 0.1-7.0), 1.0% (95% CI, 0.1-6.6), 1.1% (95% CI, 0.2-7.7), and 13.4% (95% CI, 4.4-36.7) among persons with no/mild fibrosis, moderate fibrosis, severe fibrosis, and cirrhosis, respectively (P < 0.01). Five years after biopsy, 0.0% (95% CI, 0.0-14.8) of persons with no/mild fibrosis had suffered an LRD compared with 1.0% (95% CI, 0.2-7.5) of persons with moderate fibrosis, 4.7% (95% CI, 1.5-14.1) with severe fibrosis, and 16.3% (95% CI, 7.0-35.1) with cirrhosis (P < 0.01). Conclusion: For prevention of HCC, LRD, and ESLD in the short term, HCV therapy should target individuals who have more than mild fibrosis. (Hepatology 2017;66:37–45).

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.

Haemophilus influenzae serotype b (Hib) was a major cause of meningitis in children until Hib conjugate vaccine was introduced into the routine infant immunization program and Hib disease in children was almost eliminated. In Alaska, northern Canada and other countries with Indigenous peoples, H. influenzae serotype a (Hia) has emerged as a significant cause of pneumonia, meningitis and septic arthritis especially in children under 24 months of age. A joint government initiative between the Public Health Agency of Canada (PHAC) and the National Research Council of Canada (NRC) was carried out to assess whether an Hia vaccine could be developed for the common good. The initiative included strategic partnerships with clinician researchers in Thunder Bay, Ontario who provide health services to Indigenous people and the Artic Investigations Program (AIP) of the United States Centers for Disease Control and Prevention (CDC) in Alaska. This government initiated and funded research identified that the development of an Hia vaccine is possible and ongoing surveillance that includes strain characterization is essential to understand the potential spread of Hia in North America and around the world.

Background Haemophilus influenzae serotype a (Hia) is an important cause of infection among Alaska Native children. In 2018, 4 invasive Hia cases (iHia) occurred in an Alaska community. Our response aimed to prevent more iHia and evaluate Hia carriage in the community. Whole genome sequencing (WGS) was performed to compare Hia from iHia patients across Alaska in 2018, and from healthy outbreak community members. Methods We collected oropharyngeal (OP) samples from outbreak community members. Children aged < 10 years and people in close contact with cases (contacts) were offered rifampin prophylaxis. A second set of OP samples was collected 8 weeks later. Isolates from iHia from across the state were collected as part of the state surveillance. Hia was detected by PCR and culture, then characterized by antimicrobial susceptibility and WGS. Results At baseline, contacts had a higher prevalence of Hia carriage than non-contacts (4/27(14.8%) vs 7/364(1.9%), p=0.0043). Eight weeks after rifampin prophylaxis, carriage prevalence did not significantly change among contacts (5/42(11.9%) to 6/25(24%), p=0.18) or non-contacts (7/368(1.9%) to 2/114(1.8%), p=0.47). Phylogenetic analysis of 19 iHia isolates and 15 isolates from healthy outbreak community members, revealed two major clades that differed by an average of 300 core single nucleotide polymorphisms (SNPs). Invasive and carriage isolates from the outbreak community were clustered in one clade, along with 3 non-outbreak iHia isolates. Isolates from this community differed from each other by an average of 1.2 core SNPs. 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. Conclusion We found Hia carriage prevalence was highest among persons in contact with iHia cases. Long-term community carriage was not affected by rifampin prophylaxis, possibly due to staggered prophylaxis. In the outbreak community, Hia isolates from carriers were nearly genetically identical to iHia isolates. Overall, iHia isolates from Alaska in 2018 were genetically similar. The mutation conferring rifampin resistance is concerning, as rifampin is used to prophylax contacts of iHia cases. Disclosures All Authors: No reported disclosures

BackgroundBetween 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.MethodsWe 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 ResultsAt baseline, 4 of 27 (14.8%) contacts and 7 of 364 (1.9%) noncontacts (P < .01) carried Hia. Contacts aged ConclusionsHia carriage prevalence was significantly higher among contacts than noncontacts. Rifampin prophylaxis did not result in a reduction of Hia carriage prevalence in this community.

Summary of Problem Alaska Native (AN) people experience higher incidence of, and mortality from, gastric cancer compared to other U.S. populations1, 2. Compared to the general U.S. population, gastric cancer in AN people occurs at a younger age, is diagnosed at later stages, is more evenly distributed between the sexes, and is more frequently signet-ring or diffuse histology3. It is known that the prevalence of Helicobacter pylori (Hp) infection, a risk factor for gastric cancer, is high in AN people4; however, high antimicrobial resistance combined with high reinfection rates in Alaska make treatment at the population level complex5. In addition, health issues in AN people are uniquely challenging due to the extremely remote locations of many residents. A multiagency workgroup hosted a symposium in Anchorage that brought internationally-recognized experts and local leaders together to evaluate issues around gastric cancer in the AN population. The overall goal of this symposium was to identify the best strategies to combat gastric cancer in the AN population through prevention and early diagnosis.

BACKGROUND Q fever is a febrile illness caused by infection with the bacterium Coxiella burnetii. It is most often transmitted by inhalation of the bacteria after it is shed by infected livestock. Recent studies have found very high C. burnetii infection rates among marine mammals, but it is not known if shedding by marine mammals creates a risk of Q fever among humans. To better understand infection of humans with exposure to marine mammals, the prevalence of antibodies against C. burnetii in serum samples taken from Alaskan Native persons residing on the Pribilof Islands was evaluated. The Pribilof Islands support large populations of northern fur seals infected with C. burnetii that may increase the risk of exposure for island residents. METHODS Serum testing for IgG antibodies against C. burnetii (phase I and phase II) was performed, and demographic data were analysed utilizing banked serum specimens drawn from island residents from 1980 to 2000. RESULTS The overall seroprevalence rate was 11.6% (95% CI = 9.3%-14.4%; 72/621). This is higher than the previously reported 3.1% (95% CI = 2.1%-4.3%) seroprevalence for the U.S. POPULATION CONCLUSIONS These results suggest that Alaskan Native persons may be at higher risk for exposure to C. burnetii than the general US. population, possibly due to proximity to large populations of infected marine mammals.