Presence of cagPAI genes and characterization of vacA s, i and m regions in Helicobacter pylori isolated from Alaskans and their association with clinical pathologies.

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.

Population structure of invasive Streptococcus pneumoniae isolates among Alaskan children in the conjugate vaccine era, 2001 to 2013.

Here we describe the relationships between serotypes, genotypes, and antimicrobial susceptibility among isolates causing invasive pneumococcal disease in Alaskan children during the pneumococcal conjugate vaccine (PCV) era. From 2001 to 2013 we received 271 isolates representing 33 serotypes. The most common serotypes were 19A (29.5%, n= 80), 7F (12.5%, n= 34), 15B/C (6.3%, n= 17), and 22F (4.8%, n= 13). Multilocus sequence typing identified 11 clonal complexes (CC) and 45 singletons. Five CCs accounted for 52% (141/271) of the total: CC199 (21% [n= 57], serotypes 19A, 15B/C), CC191 (12.2% [n= 33], serotype 7F), CC172 (10.3% [n= 28], serotypes 19A, 23A, 23B), CC433 (4.4% [n= 12], serotype 22F), and CC100 (4.4% [n= 12], serotype 33F). The proportion of isolates nonsusceptible to erythromycin and tetracycline increased after 13-valent PCV use (14% [n= 30] versus 29% [n= 14]; P= 0.010) and (4% [n= 9] versus 22% [n= 11]; P< 0.001), respectively. The genetic diversity also increased after 13-valent PCV use (Simpson's diversity index =0.95 versus 0.91; P= 0.022).

Impact of the Pneumococcal Conjugate Vaccine and Antibiotic Use on Nasopharyngeal Colonization by Antibiotic Nonsusceptible Streptococcus pneumoniae, Alaska, 2000[FIGURE DASH]2010.

BACKGROUND: We describe the relative impact of the heptavalent pneumococcal conjugate vaccine (PCV7, introduced 2001) and antibiotic use on colonization by antibiotic-resistant pneumococci in urban Alaskan children during 2000-2010. METHODS: We obtained nasopharyngeal swab specimens from a convenience sample of children aged <5 years at clinics annually during 2000-2004 and 2008-2010. PCV7 status and antibiotic use <90 days before enrollment were determined by interview/medical records review. Pneumococci were characterized by serotype and susceptibility to penicillin (PCN). Isolates with full PCN resistance (PCN-R) or intermediate PCN resistance (PCN-I) were classified as PCN-NS. RESULTS: We recruited 3496 children (median, 452 per year). During 2000-2010, a range of 18-29% per year of children used PCN/amoxicillin (P value for trend = 0.09); the proportion age-appropriately vaccinated with PCV7 increased (0[FIGURE DASH]90%; P < 0.01). Among pneumococcal isolates, the PCV7-serotype proportion decreased (53-<1%; P < 0.01) and non[FIGURE DASH]PCV7-serotype proportion increased (43-95%; P < 0.01). PCN-R pneumococcal colonization prevalence decreased (23-9%; P < 0.01) and PCN-I pneumococcal colonization prevalence increased (13-24%; P < 0.01); overall PCN-NS pneumococcal colonization prevalence was unchanged. PCN-NS among colonizing PCV7-type and non[FIGURE DASH]PCV7-type pneumococci remained unchanged; a mean of 31% per year of PCV7-type and 10% per year of non[FIGURE DASH]PCV7-type isolates were PCN-R, and 10% per year of PCV7 and 20% per year of non[FIGURE DASH]PCV7-type isolates were PCN-I. CONCLUSIONS: Overall, PCN-NS pneumococcal colonization remained unchanged during 2000-2010 because increased colonization by predominantly PCN-I non-PCV7 serotypes offset decreased colonization by predominantly PCN-R PCV7 serotypes. Proportion PCN-NS did not increase within colonizing pneumococcal serotype groups (PCV7 vs. non-PCV7) despite stable PCN use in our population.

PCV7-induced changes in pneumococcal carriage and invasive disease burden in Alaskan children.

BACKGROUND: Changes in pneumococcal serotype-specific carriage and invasive pneumococcal disease (IPD) after the introduction of pneumococcal conjugate vaccine (PCV7) could inform serotype epidemiology patterns following the introduction of newer conjugate vaccines. METHODS: We used data from statewide IPD surveillance and annual pneumococcal carriage studies in four regions of Alaska to calculate serotype-specific invasiveness ratios (IR; odds ratio of a carried serotype's likelihood to cause invasive disease compared to other serotypes) in children <5 years of age. We describe changes in carriage, disease burden, and invasiveness between two time periods, the pre-PCV7 period (1996-2000) and the late post-PCV7 period (2006-2009). RESULTS: Incidence of IPD decreased from the pre- to post-vaccine period (95.7 vs. 57.2 cases per 100,000 children, P<0.001), with a 99% reduction in PCV7 disease. Carriage prevalence did not change between the two periods (49% vs. 50%), although PCV7 serotype carriage declined by 97%, and non-vaccine serotypes increased in prevalence. Alaska pre-vaccine IRs corresponded to pooled results from eight pre-vaccine comparator studies (Spearman's rho=0.44, P=0.002) and to the Alaska post-vaccine period (Spearman's rho=0.28, P=0.029). Relatively invasive serotypes (IR>1) caused 66% of IPD in both periods, although fewer serotypes with IR>1 remained in the post-vaccine (n=9) than the pre-vaccine period (n=13). CONCLUSIONS: After PCV7 introduction, serotype IRs changed little, and four of the most invasive serotypes were nearly eliminated. If PCV13 use leads to a reduction of carriage and IPD for the 13 vaccine serotypes, the overall IPD rate should further decline. NOTE: The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Effect of the 13-valent pneumococcal conjugate vaccine on nasopharyngeal colonization by Streptococcus pneumoniae--Alaska, 2008-2012.

BACKGROUND: In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced a 7-valent vaccine (PCV7) that contained all PCV7 serotypes plus 6 additional serotypes (PCV6+). We conducted annual surveys from 2008 to 2012 to determine the effect of PCV13 on colonization by pneumococcal serotypes. METHODS: We obtained nasopharyngeal swabs for pneumococcal identification and serotyping from residents of all ages at 8 rural villages and children age <60 months at 2 urban clinics. We conducted interviews/medical records review for all participants. RESULTS: A total of 18 207 nasopharyngeal swabs (rural = 16 098; urban = 2109) were collected. From 2008 to 2012, 84% of rural and 90% of urban children age <5 years were age-appropriately vaccinated with a PCV. Overall pneumococcal colonization prevalence remained stable among rural (66%) and urban (35%) children age <5 years, and adults age ≥18 years (14%). Colonization by PCV6+ serotypes declined significantly among rural children age <5 years, urban children age <5, and adults age ≥18 over the course of the study (25%-5%, 22%-9%, 22%-6%, respectively). CONCLUSIONS: PCV13 was rapidly introduced into the Alaska childhood immunization schedule and reduced colonization by PCV6+ serotypes among children. Unvaccinated adults also experienced comparable reductions in vaccine serotype colonization indicating substantial indirect protection from PCV13.

Migration of persons between households in rural Alaska: considerations for study design.

INTRODUCTION: Recent epidemiologic research studies in rural Alaska have examined risk factors for infectious diseases collected at the household level. Examples include the health effects of in-home piped water and household air quality. Because the exposure is measured at the household level, it is necessary to determine if participants remained in the same house throughout the course of follow-up. METHODS: We used data from a pneumococcal nasopharyngeal carriage study in 8 rural Alaska villages [3 regions; average number of persons: 642 (min 210, max 720 per village) to quantify changes in household membership and individual movements from 2008 to 2010. We define a household as a group of individuals living in a home together. Because the same households participated in carriage surveys over several years, we could determine changes on an annual basis. We calculated the percentage of households with a ≥ 1 person change in household members from year to year. Additionally, we present the percentage of individuals that changed households during consecutive years. RESULTS: In 3 regions of Alaska, the average household size was 5 persons. Between 2008 and 2009, 50% (250/497) of households had a change in their membership (≥ 1 person in-migrated or out-migrated). Fifty-three percent of households experienced some migration of their members between 2009 and 2010. A total of 27 and 15% of households had a change of ≥ 2 and ≥ 3 persons, respectively. The percentage of households with movement was similar among the 3 rural regions and varied from 42 to 63% between villages. At the individual level, an average of 11% of persons changed households between years. The group with the most movement between houses was persons 18-29 years of age (19%), and least movement was in 5-10 and 50-64 years of age (6%). There was no difference in movement by gender. CONCLUSIONS: In rural Alaska, 52% of households experienced movement of members between years and 11% of individuals change households. These are important demographic figures to consider when planning and designing studies that measure an epidemiological exposure at the household level. Power and sample size calculations should account for the loss to follow-up associated with in- and out-migration of individuals from households.

Alaska sentinel surveillance study of Helicobacter pylori isolates from Alaska Native persons from 2000 to 2008.

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.

Impact of conjugate vaccine on transmission of antimicrobial-resistant Streptococcus pneumoniae among Alaskan children.

BACKGROUND: The impact of heptavalent pneumococcal conjugate vaccine (PCV7) on transmission of antimicrobial-resistant Streptococcus pneumoniae is an important concern for countries considering PCV7 introduction. METHODS: Every winter from 2000 to 2004, as PCV7 was routinely introduced, we obtained nasopharyngeal swabs for pneumococcal culture, serotyping, and susceptibility testing from 150 children aged 3-59 months at each of 3 Anchorage, Alaska clinics. We assessed risk factors for pneumococcal carriage, including vaccination status and antimicrobial use. RESULTS: Between 2000 and 2004, 2250 nasopharyngeal swabs from 2061 infants and children were collected. The proportion of children receiving > or = 1 PCV7 vaccination increased from 0 to 89%, whereas overall pneumococcal carriage remained stable (38% versus 41%, respectively). Among S. pneumoniae carriers, we observed declines in carriage of PCV7 serotypes (from 54% to 10%, P < 0.01) and trimethoprim-sulfamethoxazole nonsusceptible strains (44% to 16%, P < 0.01), but not in PCN-nonsusceptible strains (36% versus 37%). Among PCN-nonsusceptible types, the proportion of serotype 19A strains increased from 10% to 32% (P = 0.0002). Recent beta-lactam use was stable throughout the period (29% overall), whereas trimethoprim-sulfamethoxazole use declined from 6% to 2% (P = 0.02). CONCLUSIONS: PCV7 vaccination in the first 5 years did not affect overall pneumococcal carriage, but was associated with a shift in serotype distribution from PCV7 types to non-PCV7 types. With persistent pressure of some antimicrobials, reductions in carriage of antimicrobial nonsusceptible PCV7 types may be offset by increases in carriage of nonsusceptible non-PCV7 types.

Invasive pneumococcal disease caused by nonvaccine serotypes among alaska native children with high levels of 7-valent pneumococcal conjugate vaccine coverage.

CONTEXT: With routine childhood vaccination using heptavalent pneumococcal conjugate vaccine, one concern has been the potential for emergence and expansion of replacement disease caused by serotypes not contained in the heptavalent conjugate vaccine. OBJECTIVE: To determine whether replacement disease is associated with the overall decline in invasive pneumococcal disease among Alaska Native children. DESIGN, SETTING, AND PATIENTS: Alaska statewide longitudinal population-based laboratory surveillance of invasive Streptococcus pneumoniae infections from January 1, 1995, through December 31, 2006. MAIN OUTCOME MEASURES: Incidence and types of pneumococcal disease in children younger than 2 years. RESULTS: In the first 3 years after introduction of routine vaccination with heptavalent pneumococcal conjugate vaccine, overall invasive pneumococcal disease decreased 67% in Alaska Native children younger than 2 years (from 403.2 per 100,000 in 1995-2000 to 134.3 per 100,000 per year in 2001-2003, P<.001). However, between 2001-2003 and 2004-2006, there was an 82% increase in invasive disease in Alaska Native children younger than 2 years to 244.6/100,000 (P = .02). Since 2004, the invasive pneumococcal disease rate caused by nonvaccine serotypes has increased 140% compared with the prevaccine period (from 95.1 per 100,000 in 1995-2000 to 228.6 in 2004-2006, P = .001). During the same period, there was a 96% decrease in heptavalent vaccine serotype disease. Serotype 19A accounted for 28.3% of invasive pneumococcal disease among Alaska children younger than 2 years during 2004-2006. There was no significant increase in nonvaccine disease in non-Native Alaska children younger than 2 years. CONCLUSIONS: Alaska Native children are experiencing replacement invasive pneumococcal disease with serotypes not covered by heptavalent pneumococcal conjugate vaccine. The demonstration of replacement invasive pneumococcal disease emphasizes the importance of ongoing surveillance and development of expanded valency vaccines.

Dynamics of Helicobacter pylori-specific immunoglobulin G for 2 years after successful eradication of Helicobacter pylori infection in an American Indian and Alaska Native population.

Helicobacter pylori antibodies were measured over 24 months in American Indian and Alaska Native persons who cleared their infections. Two months after treatment, 82% of H. pylori-negative persons remained seropositive. While there were declines in H. pylori antibodies for 12 months, after 24 months 71% of persons remained seropositive.

The relationship between previous fluoroquinolone use and levofloxacin resistance in Helicobacter pylori infection.

The relationship between prior fluoroquinolone use and levofloxacin resistance in Helicobacter pylori infection is unknown. Among 125 enrolled patients, 8.8% had H. pylori isolates that were resistant to levofloxacin. Levofloxacin resistance was associated with any prior fluoroquinolone use over the previous 10 years and with the total number of fluoroquinolone courses prescribed (P<.001).

Alaska sentinel surveillance for antimicrobial resistance in Helicobacter pylori isolates from Alaska native persons, 1999-2003.

BACKGROUND: Previous studies in Alaska have demonstrated elevated proportions of antimicrobial resistance among Helicobacter pylori isolates. MATERIALS AND METHODS: We analyzed H. pylori data from the Centers for Disease Control and Prevention (CDC)'s sentinel surveillance in Alaska from July 1999 to June 2003 to determine the proportion of culture-positive biopsies from Alaska Native persons undergoing routine upper-endoscopy, and the susceptibility of H. pylori isolates to metronidazole [minimum inhibitory concentration (MIC) of > 8 g metronidazole/mL), clarithromycin (MIC > or = 1), tetracycline (MIC > or = 2) and amoxicillin (MIC > or = 1)] using agar dilution. RESULTS: Nine-hundred sixty-four biopsy specimens were obtained from 687 participants; 352 (51%) patients tested culture positive. Mean age of both culture-positive and culture-negative patients was 51 years. Metronidazole resistance was demonstrated in isolates from 155 (44%) persons, clarithromycin resistance from 108 (31%) persons, amoxicillin resistance from 8 (2%) persons, and 0 for tetracycline resistance. Metronidazole and clarithromycin resistance varied by geographic region. Female patients were more likely than male subjects to show metronidazole resistance (p < .01) and clarithromycin resistance (p = .05). CONCLUSIONS: Resistance to metronidazole and clarithromycin is more common among H. pylori isolates from Alaska Native persons when compared with those from elsewhere in the USA.

Indirect effect of conjugate vaccine on adult carriage of Streptococcus pneumoniae: an explanation of trends in invasive pneumococcal disease.

BACKGROUND: Use of heptavalent protein-polysaccharide pneumococcal conjugate vaccine (PCV7) has been associated with decreases in PCV7-type invasive pneumococcal disease and nasopharyngeal (NP) carriage in children. Vaccine use has also indirectly decreased the rate of invasive disease in adults, presumably through decreased transmission of pneumococci from vaccinated children to adults. METHODS: We conducted NP carriage surveys in 8 villages in Alaska in 1998-2004. Streptococcus pneumoniae isolates were characterized by serotype and antimicrobial susceptibility. We analyzed trends in serotype distribution, antibiotic resistance, and factors associated with adult carriage of PCV7-serotype pneumococci before and after the introduction of PCV7 in 2001. RESULTS: We collected 15,598 NP swabs; overall, 52% of adults living in the villages surveyed participated in the colonization study. The proportion of adult carriers with PCV7-type pneumococcal carriage decreased from 28% of carriers in 1998-2000 to 4.5% of carriers in 2004 (P<.0001). Among adults, the proportion of colonizing isolates that were resistant to penicillin decreased from 13% in 1998-2000 to 6% in 2004 (P=.05), whereas the percentage of isolates with intermediate susceptibility to penicillin increased from 12% in 1998-2000 to 19% in 2004 (P<.01). Adults were more likely to carry PCV7-type pneumococci if they lived with a child <5 years old or if they lived with a child who had not been age-appropriately vaccinated with PCV7. CONCLUSIONS: Pediatric vaccination with PCV7 has resulted in decreased PCV7-type pneumococcal carriage among adults and helps to explain recent decreases in the rate of PCV7-type invasive pneumococcal disease among adults.

Impact of heptavalent pneumococcal conjugate vaccine on invasive disease, antimicrobial resistance and colonization in Alaska Natives: progress towards elimination of a health disparity.

We evaluated invasive pneumococcal disease (IPD), antimicrobial resistance and nasopharyngeal colonization before and after introduction of pneumococcal conjugate vaccine (PCV7) in Alaska Natives (AN), a population with high IPD rates. We obtained IPD rates from population-based surveillance. Colonization was determined from annual surveys among rural AN of all ages and from urban children. After vaccine introduction, vaccine-type IPD rates declined by 91% among AN children <2 years, by 80% among non-Natives <2 years, and by 40% for adults of all races (P<0.001 each). IPD decreased for isolates resistant to penicillin, erythromycin and cotrimoxazole (P<0.001 each). Vaccine-type colonization decreased among rural and urban children <5 years and among rural adults (P<0.001 each). PCV7 vaccine has eliminated a longstanding disparity of vaccine-type IPD for AN children. Decreased vaccine-type colonization and IPD in adults demonstrate indirect vaccine effects.

The relationship among previous antimicrobial use, antimicrobial resistance, and treatment outcomes for Helicobacter pylori infections.

BACKGROUND: The relationship between previous antimicrobial treatments and infection with drug-resistant Helicobacter pylori is unknown. OBJECTIVES: To determine whether previous use of antimicrobial agents predicts subsequent antibiotic resistance of H. pylori and whether resistance affects treatment outcome. DESIGN: Retrospective cohort analysis of adults recruited sequentially from a clinical practice. SETTING: A referral hospital in Anchorage, Alaska. PATIENTS: 125 adults infected with H. pylori. MEASUREMENTS: Medical records were reviewed for antimicrobial agents prescribed in the 10 years before diagnosis with H. pylori infection. Antimicrobial susceptibility of H. pylori isolates obtained from endoscopic gastric biopsy was determined by using agar dilution. Cure was determined by using the urea breath test 2 months after antimicrobial treatment. RESULTS: Among the 125 patients, 37 (30%) were found to have H. pylori isolates resistant to clarithromycin and 83 (66%) were found to have H. pylori isolates resistant to metronidazole. Resistance to clarithromycin was associated with previous use of any macrolide antibiotic (P < 0.001), and resistance to metronidazole was associated with previous use of metronidazole (P < 0.001). The odds of isolates being resistant to clarithromycin increased in relation to the number of courses of macrolides received (P < 0.001). Among 53 persons treated with clarithromycin-based regimens, treatment failed in 77% of those carrying clarithromycin-resistant H. pylori (10 of 13) and 13% of those with clarithromycin-susceptible strains (5 of 40) (relative risk, 6.2 [95% CI, 1.9 to 37.1]; P < 0.001). CONCLUSIONS: Previous use of macrolides and metronidazole is associated with H. pylori resistant to these antimicrobial agents. Clarithromycin resistance is associated with a greater risk for failure with clarithromycin-based treatments.