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: Adults aged ≥65 years, adults with certain underlying medical conditions, and persons experiencing homelessness are at increased risk for invasive pneumococcal disease (IPD). Two new pneumococcal conjugate vaccines, 15-valent pneumococcal conjugate vaccine (PCV15) and 20-valent pneumococcal conjugate vaccine (PCV20), were recently approved for use in U.S. adults. We described the epidemiology of IPD among Alaska adults and estimated the proportion of IPD cases potentially preventable by new vaccines. METHODS: We used statewide, laboratory-based surveillance data to calculate and compare IPD incidence rates and 95% confidence intervals (CI) among Alaska adults aged ≥18 years during 2011-2020 and estimate the proportion of IPD cases that were caused by serotypes in PCV15 and PCV20. RESULTS: During 2011-2020, 1,164 IPD cases were reported among Alaska adults for an average annual incidence of 21.3 cases per 100,000 adults per year (95% CI: 20.1-22.5). Incidence increased significantly during the study period (p<0.01). IPD incidence among Alaska Native adults was 4.7 times higher than among non-Alaska Native adults (95% CI: 4.2-5.2). Among adults experiencing homelessness in Anchorage, IPD incidence was 72 times higher than the general adult population (95% CI: 59-89). Overall, 1,032 (89%) Alaska adults with IPD had an indication for pneumococcal vaccine according to updated vaccination guidelines; 456 (39%) and 700 (60%) cases were caused by serotypes in PCV15 and PCV20, respectively. CONCLUSIONS: Use of PCV15 and PCV20 could substantially reduce IPD among adults in Alaska, including Alaska Native adults and adults experiencing homelessness.

BACKGROUND: Haemophilus influenzae serotype a (Hia) can cause severe invasive disease, especially in young children. In 2018, four 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 (15) and invasive (4) Hia isolates from the outbreak community, together with 15 non-outbreak 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 two major clades that differed by an average of 300 core single nucleotide polymorphisms (SNPs). All isolates from the outbreak community were clustered in one subclade, within a larger clade containing 3 non-outbreak 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.

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.

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.

Background: Helicobacter pylori isolates from Alaska have demonstrated a high prevalence of antimicrobial resistance. Objective(s): To determine treatment failure in three groups, and analyse the relationship between treatment failure and antimicrobial resistance. Method(s): Antimicrobial susceptibility was determined using agar dilution and Etest. Treatment success was determined using the urea breath test 2 months after antimicrobial therapy. Result(s): Among 303 treated adult patients, 103 (34%) failed initial treatment despite a 91% compliance with medication. About 222 (73%) patients were treated with a clarithromycin-based regimen, 55 (18%) with a metronidazole-based regimen, 15 (5%) with a regimen that contained clarithromycin and metronidazole and 11 (4%) with other antimicrobials. Among 260 culture-positive patients, 156 (60%) were infected with metronidazole-resistant isolates, 74 (28%) clarithromycin-resistant, 52 (20%) clarithromycin/metronidazole-resistant, 40 (15%) levofloxacin-resistant, 11 (4%) clarithromycin/metronidazole/levofloxacin-resistant and nine (3%) amoxicillin-resistant. Overall, 34% of patients were treated with at least one antibiotic to which their infecting organism was resistant. Among patients treated with clarithromycin-based regimens, treatment failed in 72% of patients carrying clarithromycin-resistant H pylori vs 20% with clarithromycin-sensitive strains (RR = 3.7, P < 0.001). Among patients treated with metronidazole-based regimens, treatment failed in 19% of patients carrying metronidazole-resistant H pylori vs 24% with metronidazole-sensitive strains (P = 0.72). Conclusion(s): A high proportion of H pylori isolates demonstrate resistance to clarithromycin, metronidazole or levofloxacin. Over one third of H pylori-infected patients were treated with an antibiotic to which their infecting organism demonstrated resistance. Clarithromycin resistance is associated with a greater risk for failure with clarithromycin-based multidrug regimens compared to clarithromycin-sensitive; resistance to metronidazole did not affect treatment failure.

OBJECTIVES: Alaska Native people experience a high burden of Helicobacter pylori infection and concomitant high rates of gastric cancer. Additionally, the prevalence of antimicrobial resistant strains of H. pylori has been shown to be high in Alaska. We evaluated antimicrobial resistance over time among sentinel surveillance isolates and assessed risk factors for carrying resistant H. pylori. METHODS: Through Alaska's H. pylori sentinel surveillance system, we collected and cultured antral and fundal biopsies from Alaska Native patients undergoing esophagogastroduodenoscopy for clinical indications during 2000-2016. For positive cultures, we performed minimum inhibitory concentration (MIC) testing for metronidazole, amoxicillin, clarithromycin, tetracycline, and levofloxacin. RESULTS: We tested 800H. pylori isolates obtained from 763 patients. Metronidazole resistance was most common (342/800; 43%), followed by clarithromycin resistance (238/800; 30%), resistance to both clarithromycin and metronidazole (128/800; 16%), and levofloxacin resistance (113/800; 15%). Low proportions of isolates were resistant to amoxicillin and tetracycline. Levofloxacin resistance increased between 2000 and 2016 (p <0.001), but resistance to other antimicrobials did not change over time. Metronidazole and clarithromycin resistance were more common among women (p <0.001 for both), while levofloxacin resistance was more common among those with an urban residence (p=0.003). Metronidazole resistance and levofloxacin resistance were more common among older patients (p=0.004, p=0.012). CONCLUSION: Between 2000 and 2016, a large percentage of the H. pylori isolates received by the Alaska Sentinel Surveillance System demonstrated resistance to common antimicrobial agents. The surveillance system provides valuable information for clinicians to make informed treatment choices for patient with H. pylori.

The Arctic Investigations Program (AIP) began surveillance for invasive group A streptococcal (GAS) infections in Alaska in 2000 as part of the invasive bacterial diseases population-based laboratory surveillance program. Between 2001 and 2013, there were 516 cases of GAS infection reported, for an overall annual incidence of 5.8 cases per 100,000 persons with 56 deaths (case fatality rate, 10.7%). Of the 516 confirmed cases of invasive GAS infection, 422 (82%) had isolates available for laboratory analysis. All isolates were susceptible to penicillin, cefotaxime, and levofloxacin. Resistance to tetracycline, erythromycin, and clindamycin was seen in 11% (n = 8), 5.8% (n = 20), and 1.2% (n = 4) of the isolates, respectively. A total of 51 emm types were identified, of which emm1 (11.1%) was the most prevalent, followed by emm82 (8.8%), emm49 (7.8%), emm12 and emm3 (6.6% each), emm89 (6.2%), emm108 (5.5%), emm28 (4.7%), emm92 (4%), and emm41 (3.8%). The five most common emm types accounted for 41% of isolates. The emm types in the proposed 26-valent and 30-valent vaccines accounted for 56% and 78% of all cases, respectively. GAS remains an important cause of invasive bacterial disease in Alaska. Continued surveillance of GAS infections will help improve understanding of the epidemiology of invasive disease, with an impact on disease control, notification of outbreaks, and vaccine development.

We performed a study to determine rates of reinfection in three groups followed for 2 years after successful treatment: American Indian/Alaska Native (AI/AN) persons living in urban (group 1) and rural (group 2) communities, and urban Alaska non-Native persons (group 3). We enrolled adults diagnosed with H. pylori infection based on a positive urea breath test (13C-UBT). After successful treatment was documented at 2 months, we tested each patient by 13C-UBT at 4, 6, 12 and 24 months. At each visit, participants were asked about medication use, illnesses and risk factors for reinfection. We followed 229 persons for 2 years or until they became reinfected. H. pylori reinfection occurred in 36 persons; cumulative reinfection rates were 14.5%, 22.1%, and 12.0% for groups 1, 2, and 3, respectively. Study participants who became reinfected were more likely to have peptic ulcer disease (P = 0.02), low education level (P = 0.04), or have a higher proportion of household members infected with H. pylori compared to participants who did not become reinfected (P = 0.03). Among all three groups, reinfection occurred at rates higher than those reported for other US populations (<5% at 2 years); rural AI/AN individuals appear to be at highest risk for reinfection.

The rapid emergence of antibiotic-resistant pneumococcal strains has reduced treatment options. The aim of this study was to determine antimicrobial susceptibilities, serotype distributions, and molecular resistance mechanisms among macrolide-resistant invasive pneumococcal isolates in Alaska from 1986 to 2010. We identified cases of invasive pneumococcal disease in Alaska from 1986 to 2010 through statewide population-based laboratory surveillance. All invasive pneumococcal isolates submitted to the Arctic Investigations Program laboratory were confirmed by standard microbiological methods and serotyped by slide agglutination and the Quellung reaction. MICs were determined by the broth microdilution method, and macrolide-resistant genotypes were determined by multiplex PCR. Among 2,923 invasive pneumococcal isolates recovered from 1986 to 2010, 270 (9.2%) were nonsusceptible to erythromycin; 177 (66%) erythromycin-nonsusceptible isolates demonstrated coresistance to penicillin, and 167 (62%) were multidrug resistant. The most frequent serotypes among the macrolide-resistant isolates were serotypes 6B (23.3%), 14 (20.7%), 19A (16.7%), 9V (8.9%), 19F (6.3%), 6A (5.6%), and 23F (4.8%). mef and erm(B) genes were detected in 207 (77%) and 32 (12%) of the isolates, respectively. Nineteen (7%) of the erythromycin-nonsusceptible isolates contained both mef and erm(B) genotypes; 15 were of serotype 19A. There was significant year-to-year variation in the proportion of isolates that were nonsusceptible to erythromycin (P < 0.001). Macrolide resistance among pneumococcal isolates from Alaska is mediated predominantly by mef genes, and this has not changed significantly over time. However, there was a statistically significant increase in the proportion of isolates that possess both erm(B) and mef, primarily due to serotype 19A isolates.

BACKGROUND: Indigenous children in Australia and Alaska have very high rates of chronic suppurative lung disease (CSLD)/bronchiectasis. Antibiotics, including frequent or long-term azithromycin in Australia and short-term beta-lactam therapy in both countries, are often prescribed to treat these patients. In the Bronchiectasis Observational Study we examined over several years the nasopharyngeal carriage and antibiotic resistance of respiratory bacteria in these two PCV7-vaccinated populations. METHODS: Indigenous children aged 0.5-8.9 years with CSLD/bronchiectasis from remote Australia (n = 79) and Alaska (n = 41) were enrolled in a prospective cohort study during 2004-8. At scheduled study visits until 2010 antibiotic use in the preceding 2-weeks was recorded and nasopharyngeal swabs collected for culture and antimicrobial susceptibility testing. Analysis of respiratory bacterial carriage and antibiotic resistance was by baseline and final swabs, and total swabs by year. RESULTS: Streptococcus pneumoniae carriage changed little over time. In contrast, carriage of Haemophilus influenzae declined and Staphylococcus aureus increased (from 0% in 2005-6 to 23% in 2010 in Alaskan children); these changes were associated with increasing age. Moraxella catarrhalis carriage declined significantly in Australian, but not Alaskan, children (from 64% in 2004-6 to 11% in 2010). While beta-lactam antibiotic use was similar in the two cohorts, Australian children received more azithromycin. Macrolide resistance was significantly higher in Australian compared to Alaskan children, while H. influenzae beta-lactam resistance was higher in Alaskan children. Azithromycin use coincided significantly with reduced carriage of S. pneumoniae, H. influenzae and M. catarrhalis, but increased carriage of S. aureus and macrolide-resistant strains of S. pneumoniae and S. aureus (proportion of carriers and all swabs), in a 'cumulative dose-response' relationship. CONCLUSIONS: Over time, similar (possibly age-related) changes in nasopharyngeal bacterial carriage were observed in Australian and Alaskan children with CSLD/bronchiectasis. However, there were also significant frequency-dependent differences in carriage and antibiotic resistance that coincided with azithromycin use.

We investigated serotype 6A/6C invasive pneumococcal disease (IPD) incidence, genetic diversity, and carriage before and after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Alaska. IPD cases (1986-2009) were identified through population-based laboratory surveillance. Isolates were initially serotyped by conventional methods, and 6C isolates were differentiated from 6A by polymerase chain reaction. Among invasive and carriage isolates initially typed as 6A, 35% and 50% were identified as 6C, respectively. IPD rates caused by serotype 6A or 6C among children <5 years did not change from the pre- to post-PCV7 period (P = 0.71 and P = 0.09, respectively). Multilocus sequence typing of IPD isolates revealed 28 sequence types. The proportion of serotype 6A carriage isolates decreased from 7.4% pre-PCV7 to 1.8% (P < 0.001) during 2008-2009; the proportion of serotype 6C carriage isolates increased from 3.0% to 8.4% (P = 0.004) among children <5 years. Continued surveillance is warranted to monitor changes in serotype distribution and prevalence.

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

We read with interest of three Neisseria meningitidis strains recovered in Germany that reacted with commercial (Oxoid, Wesel, Germany) serogroupY and serogroup W135 antisera (3). The molecular basis of this dual antigenic specificity has been determined to be due to a single amino acid change at position 310 in the EX7E motif of the capsule polymerase enzyme synG (also referred to as siaDY) (from glycine to serine) or synF (siaDW-135) (from proline to serine) (2). Both studies confirmed our earlier report of such unusual strains causing invasive meningococcal disease (IMD) (10).

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