Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-28 (of 28 Records) |
Query Trace: Bulkow LR[original query] |
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Increasing non-susceptibility to antibiotics within carried pneumococcal serotypes - Alaska, 2008-2015
Plumb ID , Gounder PP , Bruden DJT , Bulkow LR , Rudolph KM , Singleton RJ , Hennessy TW , Bruce MG . Vaccine 2020 38 (27) 4273-4280 BACKGROUND: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. |
Transplacental respiratory syncytial virus and influenza virus antibody transfer in Alaska Native and Seattle mother-infant pairs
Chu HY , Newman KL , Englund JA , Cho S , Bull C , Lacombe K , Carlin K , Bulkow LR , Rudolph K , DeByle C , Berner J , Klejka J , Singleton R . J Pediatric Infect Dis Soc 2020 10 (3) 230-236 BACKGROUND: Alaska Native (AN) infants are at risk for severe disease due to respiratory syncytial virus (RSV) and influenza. Maternal immunization protects young infants through transplacental antibody transfer. RSV- and influenza-specific transplacental antibody transfer in mother-infant pairs has not previously been evaluated in the AN population. METHODS: Serum samples collected during pregnancy and at birth from AN mother-infant pairs in the Yukon-Kuskokwim Delta region (YKD) of Alaska (2000-2011; n = 75) and predominantly white pairs in Seattle, Washington (2014-2016; n = 57), were tested for RSV and influenza antibody using a microneutralization and hemagglutination inhibition assay, respectively, and compared between sites. RESULTS: Mean RSV antibody concentrations in pregnant women in YKD and Seattle were similar (log2 RSV antibody 10.6 vs 10.7, P = .86), but cord blood RSV antibody concentrations were significantly lower in infants born to mothers in YKD compared with Seattle (log2 RSV antibody 11.0 vs 12.2, P < .001). Maternal and cord blood influenza antibody concentrations were lower for women and infants in YKD compared with Seattle for all 4 influenza antigens tested (all P < .05). The mean cord to maternal RSV antibody transfer ratio was 1.15 (standard deviation [SD], 0.13) in mother-infant pairs in Seattle compared with 1.04 (SD, 0.08) in YKD. Mean cord blood to maternal antibody transfer ratios for influenza antigens ranged from 1.22 to 1.42 in Seattle and from 1.05 to 1.59 in YKD. CONCLUSIONS: Though the transplacental antibody transfer ratio was high (>1.0) for both groups, transfer ratios for RSV antibody were significantly lower in AN mother-infant pairs. Further studies are needed to elucidate the impact of lower transplacental antibody transfer on infant disease risk in rural Alaska.Alaska Native and continental US mother-infant pairs have high transplacental antibody transfer ratios (>1.0) for influenza and respiratory syncytial virus, but anti-respiratory syncytial virus antibody levels are significantly lower in Alaska Native pairs than in those from the continental US. |
Human papillomavirus (HPV) types among Alaska native women attending a colposcopy clinic in Anchorage, Alaska, 2009-2011
Murphy NJ , Bulkow LR , Steinau M , Dunne EF , Meites E , Markowitz LE , Unger ER , Hennessy TW . Infect Agent Cancer 2020 15 13 Background: The first HPV vaccines licensed targeted two HPV types responsible for most cervical cancers. A 9-valent vaccine (9vHPV), targeting 5 additional types, was introduced in 2016 and is currently the only HPV vaccine available in the United States. Previous studies demonstrated high rates of HPV infection in Alaska Native (AN) women. We sought to measure prevalence of high risk HPV types in AN women undergoing colposcopy and to determine those preventable by vaccination. Methods: For this cross-sectional study, we recruited women who were undergoing colposcopy for clinical indications at Alaska Native Medical Center to obtain cervical brush biopsy samples. Specimens were shipped to Atlanta, Georgia for DNA extraction, HPV detection, and typing using L1 PCR with type-specific hybridization to detect 37 HPV types. Results: Four hundred eighty eight specimens from 489 women were tested. At least one HPV type was found in 458 (94%) specimens. Of 458 participants who were HPV positive, 332 (72%) had two or more types. At least one type targeted by 9vHPV was detected in 95% of participants with CIN 3 (21/22), 82% with CIN 2 (37/45), and 65% with CIN 1 (119/184). (p < 0.001) HPV 16 or 18 were detected in 77% (17/22) with CIN 3, 53% (24/45) with CIN 2, and 36% (67/184) with CIN 1. (p < 0.001). Conclusions: A substantial proportion of AN women attending colposcopy clinic had evidence of HPV 16/18 infection, as well as other high risk types targeted by 9vHPV. At least one 9vHPV type was detected in 62% of the participants overall, and 95% of participants with CIN3. AN women are expected to benefit from vaccination against HPV 16/18, and will have greater benefit from 9vHPV. Information from this study could be used to develop public health strategies to increase vaccine uptake, or to track HPV genotype prevalence over time. |
The relative invasive disease potential of Streptococcus pneumoniae among children after PCV introduction: a systematic review and meta-analysis
Balsells E , Dagan R , Yildirim I , Gounder PP , Steens A , Munoz-Almagro C , Mameli C , Kandasamy R , Lavi NG , Daprai L , van der Ende A , Trzcinski K , Nzenze S , Meiring S , Foster D , Bulkow LR , Rudolph K , Valero-Rello A , Ducker S , Vestrheim DF , von Gottberg A , Pelton SI , Zuccotti G , Pollard AJ , Sanders EAM , Campbell H , Madhi SA , Nair H , Kyaw MH . J Infect 2018 77 (5) 368-378 OBJECTIVES: Burden of pneumococcal disease depends on the prevalence and invasive disease potential of serotypes. We aimed to estimate the invasive disease potential of serotypes in children under 5 years of age by combining data from different settings with routine immunisation with pneumococcal conjugate vaccines (PCV). METHODS: We conducted a systematic review, supplemented by unpublished data, to identify data on the frequency of pneumococcal serotypes in carriage and invasive pneumococcal disease (IPD). We estimated the invasive disease potential of serotypes as the ratio of IPD in relation to carriage (odds ratio and 95%CI) compared with 19A (reference serotype) by meta-analysis. We report results based on a random effects model for children aged 0-23, 24-29, and 0-59 months and by invasive clinical syndromes. RESULTS: In comparison with 19A, serotypes 1, 7F, and 12F had a significantly higher invasive disease potential in children aged 0-23 and 0-59 months for all IPD and clinical syndromes (OR>5). Several non-vaccine types (NVTs) (6C, 15A, 15BC, 16F, 23B, in these two age groups) had a lower invasive disease potential than 19A (OR 0*1-0*3). NVTs 8, 12F, 24F, and 33F were at the upper end of the invasiveness spectrum. CONCLUSIONS: There is substantial variation among pneumococcal serotypes in their potential to cause IPD and disease presentation, which is influenced by age and time after PCV introduction. Surveillance of IPD and carriage is critical to understand the expected effectiveness of current PCVs (in the longer term) and guide the development of future vaccines. |
Prevalence of Helicobacter pylori among Alaskans: Factors associated with infection and comparison of urea breath test and anti-Helicobacter pylori IgG antibodies
Miernyk KM , Bulkow LR , Gold BD , Bruce MG , Hurlburt DH , Griffin PM , Swerdlow DL , Cook K , Hennessy TW , Parkinson AJ . Helicobacter 2018 23 (3) e12482 BACKGROUND: Helicobacter pylori is one of the most common human infections in the world, and studies in Alaska Native people, as well as other Indigenous peoples, have shown a high prevalence of this gastric infection. This study was undertaken to determine the prevalence of H. pylori infection by urea breath test (UBT) and anti- H. pylori IgG among Alaskans living in four regions of the state and to identify factors associated with infection. METHODS: A convenience sample of persons > 6 months old living in five rural and one urban Alaskan community were recruited from 1996 to 1997. Participants were asked about factors possibly associated with infection. Sera were collected and tested for anti- H. pylori IgG antibodies; a UBT was administered to participants > 5 years old. RESULTS: We recruited 710 people of whom 571 (80%) were Alaska Native and 467 (66%) were from rural communities. Rural residents were more likely to be Alaska Native compared with urban residents (P < .001). Of the 710 people, 699 (98%) had a serum sample analyzed, and 634 (97%) persons > 5 years old had a UBT performed. H. pylori prevalence was 69% by UBT and 68% by anti- H. pylori IgG. Among those with a result for both tests, there was 94% concordance. Factors associated with H. pylori positivity were Alaska Native racial status, age >/= 20 years, rural region of residence, living in a crowded home, and drinking water that was not piped or delivered. CONCLUSIONS: Helicobacter pylori prevalence is high in Alaska, especially in Alaska Native persons and rural residents. Concordance between UBT and serology was also high in this group. Two socioeconomic factors, crowding and drinking water that was not piped or delivered, were found to be associated with H. pylori positivity. |
Persistence of antibody to hepatitis A virus 20 years after receipt of hepatitis A vaccine in Alaska
Plumb ID , Bulkow LR , Bruce MG , Hennessy TW , Morris J , Rudolph K , Spradling P , Snowball M , McMahon BJ . J Viral Hepat 2017 24 (7) 608-612 Hepatitis A vaccine is recommended for children ≥1 year old to prevent hepatitis A virus (HAV) infection. However the duration of vaccine-induced immunity is unknown. We evaluated a cohort of Alaska Native persons 20 years after HAV vaccination. Children aged 3-6 years had been previously randomized to receive 3 doses of HAV vaccine (360 ELISA units/dose) at: A) 0,1,2 months; B) 0,1,6 months; and C) 0,1,12 months. We measured anti-HAV antibody concentrations every 2-3 years; described geometric mean concentrations (GMC) and the proportion with protective antibody (≥20 mIU mL-1) over time; and modelled change in GMC using fractional polynomial regression. Of 144 participants, after 20 year 52 (36.1%) were available for follow-up (17, 18, 17 children in Groups A, B and C, respectively). Overall, 46 (88.5%) of 52 available participants had anti-HAV antibody concentrations ≥20mIU mL-1 and overall GMC was 107 mIU mL-1. Although GMC levels were lower in Group A (60; CI 34-104) than in Group B (110; CI 68-177), or Group C (184; CI 98-345) (B versus C: p=0.168; A versus B/C: p=0.011), there was no difference between groups after adjusting for peak antibody levels post vaccination (p=0.579). Models predicted geometric mean concentrations of 124 mIU mL-1 after 25 years, and 106 mIU mL-1 after 30 years. HAV vaccine provides protective antibody levels 20 years after childhood vaccination. Lower antibody levels in Group A may be explained by a lower initial peak response. Our results suggest a booster vaccine dose is unnecessary for at least 25-30 years. |
Letter: hepatitis B surface seroclearance does reduce the risk of hepatocellular carcinoma - authors' reply
Gounder PP , Bulkow LR , McMahon BJ . Aliment Pharmacol Ther 2016 44 (6) 650-1 Sirs, We appreciate the interest in our study from Professors Chen and Liaw and the opportunity to provide additional information.1 As we acknowledged in our paper, the wide confidence intervals for our risk estimates resulting from the relatively small number of case- and control-patients developing HCC were an important limitation to our study.2 Thus, it is possible that we failed to detect a real reduction in HCC risk because of insufficient statistical power. As requested, we recalculated the risk for developing HCC after excluding the 2 case-patients who received antiviral treatment before HBsAg seroclearance and the 32 control-patients who had received antiviral treatment. After adjusting for age at cohort entry and initial anti-hepatitis B e antibody status, we did not detect a difference in HCC risk among case-compared with control-patients after excluding patients who had received antiviral treatment (adjusted hazard ratio: 0.7; 95% confidence interval: 0.2–2.7). The effect of age at HBsAg seroclearance on risk for HCC is complex and could be partly related to the specific HBV genotypes represented in a population. It has been demonstrated that the duration of hepatitis B e antigen persistence and the risk for HCC is substantially higher for persons with HBV genotype C compared with other genotypes.3,4 The majority of patients in the study indicating an increased risk for HCC among persons aged ≥50 years at the time of HBsAg seroclearance were infected with HBV genotype C.5,6 In contrast, the majority of patients in our study population were infected with HBV genotype D. Therefore, the risk for HCC associated with a later age of HBsAg seroclearance among Alaska Native persons compared with other geographic regions is unclear because of differences in the prevalence of HBV genotypes. Furthermore, the age at HBsAg seroclearance should not affect our interpretation of the relative risk for HCC between case- and control-patients because the majority of participants acquired HBV infection in early childhood and our analysis adjusted for case-patients’ HBsAg duration prior to seroclearance. We also speculated in our paper that ongoing low-level HBV DNA replication with continued integration into the host hepatocyte could have contributed to persistent HCC risk after HBsAg seroclearance. Further study is necessary to determine the relative importance of HBV viremia early in the course of disease versus persistence of viremia after HBsAg clearance in the development of HCC. |
Hepatocellular Carcinoma Risk in Alaska Native Children and Young Adults with Hepatitis B Virus: Retrospective Cohort Analysis.
Gounder PP , Bulkow LR , Snowball M , Negus S , Spradling PR , McMahon BJ . J Pediatr 2016 178 206-213 OBJECTIVES: To evaluate the hepatocellular carcinoma (HCC) risk in Alaska Native children and young adults with hepatitis B virus (HBV). STUDY DESIGN: Retrospective analysis of a population-based cohort of Alaska Native persons with HBV followed during 1982-2012. All individuals with HBV were offered HCC screening regardless of age using alpha-fetoprotein every 6 months; persons with an elevated alpha-fetoprotein or persons at high-risk for HCC, such as cirrhosis, family history of HCC, were offered ultrasound. We calculated the HCC incidence/1000 person-years from date of cohort entry until death, diagnosis of HCC, or attaining the age of 40 years (males) or 50 years (females). RESULTS: We followed 1083 subjects with HBV (56% male) comprising 5 genotypes (A2 [12.5%], B6 [1.7%], C [5.3%], D [49.7%], F1 [18.6%], unknown [12.4%]) for a median of 23.4 years/person. We observed 22 HCC cases (incidence/1000 person-years follow-up: 1.0); 19 HCC cases among persons with genotype F1. There was no significant difference in HCC incidence between males (1.4) and females (0.6). The HCC incidence was significantly higher for persons with genotype F1 (4.4) compared with genotype A2 (0.4) and D (0.2) and remained higher among persons with HBV genotype F1 excluding persons with HCC family history/cirrhosis (1.9). CONCLUSIONS: Alaska Native children and young adults with HBV genotype F1 are at high risk for HCC and should receive HCC surveillance. For males <40 years of age and females <50 years of age with HBV in regions of the world with a high genotype F prevalence, testing/confirming genotype F can identify persons who could benefit from HCC surveillance. |
Population structure of invasive Streptococcus pneumoniae isolates among Alaskan children in the conjugate vaccine era, 2001 to 2013.
Miernyk KM , Bulkow LR , Case SL , Zulz T , Bruce MG , Harker-Jones M , Hurlburt DA , Hennessy TW , Rudolph KM . Diagn Microbiol Infect Dis 2016 86 (2) 224-30 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). |
Declines in traditional marine food intake and vitamin D levels from the 1960s to present in young Alaska Native women
O'Brien DM , Thummel KE , Bulkow LR , Wang Z , Corbin B , Klejka J , Hopkins SE , Boyer BB , Hennessy TW , Singleton R . Public Health Nutr 2016 20 (10) 1-8 OBJECTIVE: To measure the trends in traditional marine food intake and serum vitamin D levels in Alaska Native women of childbearing age (20-29 years old) from the 1960s to the present. DESIGN: We measured a biomarker of traditional food intake, the delta15N value, and vitamin D level, as 25-hydroxycholecalciferol (25(OH)D3) concentration, in 100 serum samples from 20-29-year-old women archived in the Alaska Area Specimen Bank, selecting twenty-five per decade from the 1960s to the 1990s. We compared these with measurements of red-blood-cell delta15N values and serum 25(OH)D3 concentrations from 20-29-year-old women from the same region collected during the 2000s and 2010s in a Center for Alaska Native Health Research study. SETTING: The Yukon Kuskokwim Delta region of south-west Alaska. SUBJECTS: Alaska Native women (n 319) aged 20-29 years at the time of specimen collection. RESULTS: Intake of traditional marine foods, as measured by serum delta15N values, decreased significantly each decade from the 1960s through the 1990s, then remained constant from the 1990s through the present (F 5,306=77.4, P<0.0001). Serum vitamin D concentrations also decreased from the 1960s to the present (F 4,162=26.1, P<0.0001). CONCLUSIONS: Consumption of traditional marine foods by young Alaska Native women dropped significantly between the 1960s and the 1990s and was associated with a significant decline in serum vitamin D concentrations. Studies are needed to evaluate the promotion of traditional marine foods and routine vitamin D supplementation during pregnancy for this population. |
Cost-effectiveness analysis of hepatocellular carcinoma screening by combinations of ultrasound and alpha-fetoprotein among Alaska Native people, 1983-2012
Gounder PP , Bulkow LR , Meltzer MI , Bruce MG , Hennessy TW , Snowball M , Spradling PR , Adhikari BB , McMahon BJ . Int J Circumpolar Health 2016 75 31115 BACKGROUND: The American Association for the Study of Liver Diseases (AASLD) recommends semi-annual hepatocellular carcinoma (HCC) screening using ultrasound (US) in persons with chronic hepatitis B (CHB) virus infection at high risk for HCC such as Asian males aged ≥40 years and Asian females aged ≥50 years. OBJECTIVE: To analyse the cost-effectiveness of 2 HCC screening methods in the Alaska Native (AN) health system: US-alone, or screening by alpha-fetoprotein (AFP) initially and switching to US for subsequent screenings if AFP >10 ng/mL (AFP-->US). DESIGN: A spreadsheet-based model was developed for accounting the costs of 2 hypothetical HCC screening methods. We used epidemiologic data from a cohort of 839 AN persons with CHB who were offered HCC screening by AFP/US semi-annually during 1983-2012. We assumed that compared with AFP-->US, US-alone identifies 33% more tumours at an early stage (defined as a single tumour ≤5 cm or ≤3 tumours ≤3 cm in diameter). Years of life gained (YLG) attributed to screening was estimated by comparing additional years of survival among persons with early- compared with late-stage tumours. Screening costs were calculated using Medicare reimbursement rates in 2012. Future screening costs and YLG were projected over a 30-year time horizon using a 3% discount rate. RESULTS: The total cost of screening for the cohort by AFP-->US would have been approximately $357,000 ($36,000/early-stage tumour detected) compared to $814,000 ($59,000/early-stage tumour detected) by US-alone. The AFP-->US method would have yielded an additional 27.8 YLG ($13,000/YLG) compared with 38.9 YLG ($21,000/YLG) for US-alone. Screening by US-alone would incur an additional $114,000 per extra early-tumour detected compared with AFP-->US and $41,000 per extra YLG. CONCLUSIONS: Although US-alone HCC screening might have yielded more YLG than AFP-->US, the reduced costs of the AFP-->US method could expand access to HCC screening in resource constrained settings. |
Nested case-control study: hepatocellular carcinoma risk after hepatitis B surface antigen seroclearance
Gounder PP , Bulkow LR , Snowball M , Negus S , Spradling PR , Simons BC , McMahon BJ . Aliment Pharmacol Ther 2016 43 (11) 1197-207 BACKGROUND: Hepatocellular carcinoma (HCC) risk after resolving chronic hepatitis B virus (HBV) infection is unclear. AIM: To compare HCC risk between Alaska Native (AN) patients with and without hepatitis B surface antigen (HBsAg) seroclearance. METHODS: We selected persons with (case-patients) and without (control-patients) HBsAg seroclearance from a cohort of 1346 chronically HBV-infected AN patients followed during 1982-2013. We attempted to match two control-patients/case-patient on sex, HBV genotype, and age. Person-years of follow-up for case-patients began on the date of HBsAg resolution and for control-patients began on the date equivalent to the cohort entry date plus the years of HBsAg duration for their corresponding case-patient. We compared HCC risk using a Cox proportional hazards model. RESULTS: The 238 case-patients (4 with HCC) and 435 control-patients (9 with HCC) were similar in age [P-value (P) = 0.30], sex (P = 0.53) and HBV genotype (P = 0.99). Case-patients had longer person-years of follow-up than control-patients (11.7 vs. 10.1 years; P = 0.04). The HCC rate/100 000 persons was similar between case- (132) and control-patients (178; P = 0.65). The adjusted hazard ratio comparing case- and control-patients was similar for HCC [0.7; 95% confidence interval (CI): 0.2-2.4], increased for each 1-year increment for age (1.1; CI: 1.0-1.1; P < 0.01), and was greater if the initial HBeAg was positive (3.5; CI: 1.1-11.0; P = 0.03). CONCLUSIONS: Hepatitis B surface antigen seroclearance was not associated with reduced HCC risk; the HCC risk estimates are limited by wide 95% confidence intervals. Persons meeting HCC surveillance indications prior to HBsAg seroclearance could benefit from continued surveillance after seroclearance. |
A survey of knowledge, attitudes, and practices towards skin and soft tissue infections in rural Alaska
Raczniak GA , Gaines J , Bulkow LR , Kinzer MH , Hennessy TW , Klejka JA , Bruce MG . Int J Circumpolar Health 2016 75 30603 BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus and methicillin-sensitive S. aureus infections are common to south-western Alaska and have been associated with traditional steambaths. More than a decade ago, recommendations were made to affected communities that included preventive skin care, cleaning methods for steambath surfaces, and the use of protective barriers while in steambaths to reduce the risk of S. aureus infection. OBJECTIVE: A review of community medical data suggested that the number of skin infection clinical encounters has increased steadily over the last 3 years and we designed a public health investigation to seek root causes. STUDY DESIGN: Using a mixed methods approach with in-person surveys, a convenience sample (n=492) from 3 rural communities assessed the range of knowledge, attitudes and practices concerning skin infections, skin infection education messaging, prevention activities and home self-care of skin infections. RESULTS: We described barriers to implementing previous recommendations and evaluated the acceptability of potential interventions. Prior public health messages appear to have been effective in reaching community members and appear to have been understood and accepted. We found no major misconceptions regarding what a boil was or how someone got one. Overall, respondents seemed concerned about boils as a health problem and reported that they were motivated to prevent boils. We identified current practices used to avoid skin infections, such as the disinfection of steambaths. We also identified barriers to engaging in protective behaviours, such as lack of access to laundry facilities. CONCLUSIONS: These findings can be used to help guide public health strategic planning and identify appropriate evidence-based interventions tailored to the specific needs of the region. |
Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta-analysis
Shi T , Balsells E , Wastnedge E , Singleton R , Rasmussen ZA , Zar HJ , Rath BA , Madhi SA , Campbell S , Vaccari LC , Bulkow LR , Thomas ED , Barnett W , Hoppe C , Campbell H , Nair H . J Glob Health 2015 5 (2) 020416 BACKGROUND: Respiratory syncytial virus (RSV) is the most common pathogen identified in young children with acute lower respiratory infection (ALRI) as well as an important cause of hospital admission. The high incidence of RSV infection and its potential severe outcome make it important to identify and prioritise children who are at higher risk of developing RSV-associated ALRI. We aimed to identify risk factors for RSV-associated ALRI in young children. METHODS: We carried out a systematic literature review across 4 databases and obtained unpublished studies from RSV Global Epidemiology Network (RSV GEN) collaborators. Quality of all eligible studies was assessed according to modified GRADE criteria. We conducted meta-analyses to estimate odds ratios with 95% confidence intervals (CI) for individual risk factors. RESULTS: We identified 20 studies (3 were unpublished data) with "good quality" that investigated 18 risk factors for RSV-associated ALRI in children younger than five years old. Among them, 8 risk factors were significantly associated with RSV-associated ALRI. The meta-estimates of their odds ratio (ORs) with corresponding 95% confidence intervals (CI) are prematurity 1.96 (95% CI 1.44-2.67), low birth weight 1.91 (95% CI 1.45-2.53), being male 1.23 (95% CI 1.13-1.33), having siblings 1.60 (95% CI 1.32-1.95), maternal smoking 1.36 (95% CI 1.24-1.50), history of atopy 1.47 (95% CI 1.16-1.87), no breastfeeding 2.24 (95% CI 1.56-3.20) and crowding 1.94 (95% CI 1.29-2.93). Although there were insufficient studies available to generate a meta-estimate for HIV, all articles (irrespective of quality scores) reported significant associations between HIV and RSV-associated ALRI. CONCLUSIONS: This study presents a comprehensive report of the strength of association between various socio-demographic risk factors and RSV-associated ALRI in young children. Some of these amenable risk factors are similar to those that have been identified for (all cause) ALRI and thus, in addition to the future impact of novel RSV vaccines, national action against ALRI risk factors as part of national control programmes can be expected to reduce burden of disease from RSV. Further research which identifies, accesses and analyses additional unpublished RSV data sets could further improve the precision of these estimates. |
Persistence of seropositivity among persons vaccinated for hepatitis A during infancy by maternal antibody status: 15-year follow-up
Spradling PR , Bulkow LR , Negus SE , Homan C , Bruce MG , McMahon BJ . Hepatology 2015 63 (3) 703-11 The effect of passively transferred maternal antibody to hepatitis A virus (anti-HAV) on the duration of seropositivity after hepatitis A vaccination during infancy and early childhood is unclear. We obtained levels of anti-HAV at intervals through ages 15-16 years among three groups of Alaskan Native children who initiated a two-dose inactivated hepatitis A vaccination series at ages 6 (Group 1), 12 (Group 2), and 15 months (Group 3), each group randomized according to maternal anti-HAV status. Seropositivity (anti-HAV ≥20 mIU/mL) 30 years after the second vaccine dose among the three groups was predicted using a random effects model. One hundred eighty-three children participated in the study; follow-up did not differ significantly by vaccine group or maternal anti-HAV status. Although the frequency of seropositivity among all participants through age 10 years was high (100% among Groups 2/3 and >90% among Group 1 children), there was a decrease thereafter through ages 15-16 years among Group 1 children, who initiated vaccination at age 6 months (50%-75%), and among maternal anti-HAV-positive children in Groups 2 and 3 (67%-87%), who initiated vaccination at ages 12 and 15 months, respectively. Nonetheless, the model indicated that anti-HAV seropositivity should persist for ≥30 years after vaccination in 64% of all participants; among those seropositive at ages 15-16 years, 84% were predicted to remain so for ≥30 years. CONCLUSIONS: Most children vaccinated during early childhood available for sampling maintained seropositivity through ages 15-16 years; however, seropositivity was less frequent among those starting vaccination at age 6 months and among maternal antibody-positive participants who started vaccination at age 12 or 15 months. Overall, our findings support current vaccine recommendations and continued follow-up of this cohort. |
Eighteen years of respiratory syncytial virus surveillance: changes in seasonality and hospitalization rates in southwestern Alaska native children
Bruden DJ , Singleton R , Hawk CS , Bulkow LR , Bentley S , Anderson LJ , Herrmann L , Chikoyak L , Hennessy TW . Pediatr Infect Dis J 2015 34 (9) 945-50 BACKGROUND: Alaska Native (AN) infants from the Yukon-Kuskokwim Delta (YKD) experienced respiratory syncytial virus (RSV) hospitalization rates five times higher and an RSV season twice as long as the general US infant population. We describe trends in hospitalization rates and seasonality during 18 years of continuous RSV surveillance in this population and explore contributions of climate and sociodemographic factors. METHODS: We abstracted clinical and RSV test information from computerized medical records at YKD Regional Hospital and Alaska Native Medical Center from 1994-2012 to determine hospitalization rates and RSV season timing. Descriptive village and weather data were acquired through the US Census and Alaska Climate Research Center, University of Alaska, Fairbanks, respectively. RESULTS: During 1994-2012, YKD infant RSV hospitalization rates declined nearly 3-fold, from 177/1,000 infants/year to 65. RSV season onset shifted later, from mid-October to late December, contributing to a significantly decreased season duration, from 30 weeks to 11 weeks. In a multivariate analysis, children from villages with more crowded households and lacking plumbed water had higher rates of RSV hospitalizations (RR 1.17, p=0.0005, and RR 1.45, p=0.0003). No association of temperature or dew point was found with the timing or severity of RSV season. CONCLUSIONS: Although the RSV hospitalization rate decreased 3-fold, YKD infants still experience a hospitalization rate 3-fold higher than the general US infant population. Overcrowding and lack of plumbed water were associated with RSV hospitalization. Dramatic changes occurred in RSV seasonality, not explained by changes in climate. |
Hepatitis B antibody levels seven to nine years following booster vaccination in Alaska Native persons
Keck JW , Bulkow LR , Raczniak GA , Negus SE , Zanis CL , Bruce MG , Spradling PR , Teshale EH , McMahon BJ . Clin Vaccine Immunol 2014 21 (9) 1339-42 BACKGROUND: Hepatitis B antibody persistence was assessed in individuals who had previously received a vaccine booster. METHODS: We measured hepatitis B surface antigen antibody (anti-HBs) levels 7-9 years post-hepatitis B booster in individuals with primary vaccination at birth. RESULTS: While 95 (91.3%) of 104 participants had detectable anti-HBs (minimum 0.1 mIU/mL, maximum 1029 mIU/mL), only 43 (41%) had protective levels ≥10mIU/mL. Pre- and four week post-booster anti-HBs levels were significant predictors of hepatitis B immunity at follow-up (P <0.001). CONCLUSIONS: Almost all participants had detectable anti-HBs 7-9 years after hepatitis B vaccine booster, but less than half had levels ≥10mIU/mL. |
The 13-valent pneumococcal conjugate vaccine for invasive pneumococcal disease in Alaska Native children: results of a clinical trial
Singleton R , Wenger J , Klejka JA , Bulkow LR , Thompson A , Sarkozy D , Emini EA , Gruber WC , Scott DA . Pediatr Infect Dis J 2012 32 (3) 257-63 BACKGROUND: During 1996-2000, Alaska Native (AN) children aged <5 years from Yukon Kuskokwim Delta (YKD) had invasive pneumococcal disease (IPD) rates 10-fold higher than non-AN children (547/100,000/year vs. 56/100,000/year). After 7-valent pneumococcal conjugate vaccine (PCV7) introduction, IPD rates decreased to 148/100,000 during 2001-2004, increasing to 426/100,000 during 2005-2007 due to non-vaccine serotype disease. In 2009, we evaluated safety, immunogenicity, and impact of 13-valent pneumococcal conjugate vaccine (PCV13) in YKD children. METHODS: In a pre-licensure open-label clinical trial, eligible YKD children aged <5 years were offered PCV13 as appropriate for age and prior PCV7 history. PCV13 impact was assessed using existing Alaska-wide IPD surveillance. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) levels were measured postinfant series and posttoddler dose in a subset of subjects. Adverse events (AEs) and serious AEs were collected in all; local reactions and systemic events were collected in toddlers. All YKD children were offered licensed PCV13 when it became available. RESULTS: 372 subjects received PCV13 during the clinical trial and 3342 post-licensure (4/2010-8/2011). AEs were typically mild, or generally consistent with common childhood illnesses. IgG levels following PCV13 were similar to other populations. In YKD children aged <5 years, 52 IPD cases (31 PCV13-serotype) occurred during 2005-2008 (399.0/100,000/year), versus 9 (7 PCV13-serotype) during 1/2009-8/2011 (106.7/100,000/year; P < 0.001). No PCV13-serotype cases occurred among PCV13 recipients (3680 person follow-up years). CONCLUSIONS: PCV13 IPD incidence declined significantly after PCV13 introduction. Although non-PCV13 IPD also declined significantly, absence of PCV13 IPD in children who received PCV13 suggests a protective vaccine effect. |
Risk factors for hospitalization with lower respiratory tract infections in children in rural Alaska
Bulkow LR , Singleton RJ , Debyle C , Miernyk K , Redding G , Hummel KB , Chikoyak L , Hennessy TW . Pediatrics 2012 129 (5) e1220-7 OBJECTIVE: Lower respiratory tract infections (LRTIs) are a major cause of morbidity for children worldwide and particularly for children from developing and indigenous populations. In this study, we evaluated risk factors for hospitalization with LRTI in a region in southwest Alaska. METHODS: The study was conducted from October 1, 2006, to September 30, 2007, in the Yukon Kuskokwim Delta region of Alaska. Cases were recruited from children <3 years of age hospitalized with LRTI. Controls were recruited during visits to the surrounding communities in the region and matched posthoc to cases on the basis of subregion, season, and age. Parents were interviewed for potential risk factors, and medical records were reviewed. Participants had a nasopharyngeal swab sample taken for polymerase chain reaction (PCR) testing for a panel of respiratory viruses. Samples positive for respiratory syncytial virus, human metapneumovirus, or parainfluenza type 3 were quantitated by reverse transcriptase real-time quantitative PCR. RESULTS: One hundred twenty-eight cases were matched to 186 controls. In a multivariable conditional logistic regression model, significantly (P < .05) increased risk of hospitalization was associated with medically high-risk status, having a woodstove in the house, being bottle fed, and vomiting after feeding; living in a house that had 2 or more rooms with sinks was a protective factor. Viral loads in hospitalized cases were significantly higher than those in controls, but a strict cutoff level was not observed. CONCLUSIONS: Several risk factors for LRTI hospitalization were identified in this high risk population. Some factors are amenable to environmental and behavioral interventions. |
Persistence of hepatitis A vaccine induced seropositivity in infants and young children by maternal antibody status: 10-year follow-up
Sharapov UM , Bulkow LR , Negus SE , Spradling PR , Homan C , Drobeniuc J , Bruce M , Kamili S , Hu DJ , McMahon BJ . Hepatology 2012 56 (2) 516-22 Persistence of seropositivity conferred by hepatitis A vaccine administered to children under 2 years of age is unknown and passively transferred maternal antibodies to hepatitis A virus (maternal anti-HAV) may lower the infant's immune response to the vaccine. Infants and young children (N=197) were randomized into three groups to receive a two dose hepatitis A vaccine (HAVRIX, GlaxoSmithKline; 720 EL.U. in 0.5 ml): group 1 at 6 and 12 months, group 2 at 12 and 18 months, and group 3 at 15 and 21 months of age; within each group infants were randomized by maternal anti-HAV status. Anti-HAV levels were measured at 1 and 6 months, and at 3, 5, 7 and 10 years after second dose of hepatitis A vaccination. Children in all groups had evidence of seroprotection (>10 mIU/mL) at 1 month after dose 2. At 10 years, all children retained seroprotective anti-HAV levels except for only 7% and 11% of children in group 1 born to anti-HAV negative and anti-HAV positive mothers, respectively and 4% of group 3 children born to anti-HAV negative mothers. At 10 years, children born to anti-HAV-negative mothers in Group 3 had highest geometric mean concentration (GMC) (97 mIU/mL, 95% CI: 71-133) and children born to anti-HAV-positive mothers in Group 1 had lowest GMC (29 mIU/mL, 95% CI: 20, 4052). Anti-HAV levels through 10 years of age correlated with initial peak anti-HAV levels (tested at 1 month after second dose). CONCLUSION: The seropositivity induced by hepatitis A vaccine given to children < 2 years of age persists for at least 10 years regardless of presence of maternal anti-HAV. (HEPATOLOGY 2012.). |
Elimination of hepatocellular carcinoma and acute hepatitis B in children 25 years after a hepatitis B newborn and catch-up immunization program
McMahon BJ , Bulkow LR , Singleton RJ , Williams J , Snowball M , Homan C , Parkinson AJ . Hepatology 2011 54 (3) 801-7 Alaska Native people experienced the highest rates of acute and chronic hepatitis B virus (HBV) infection, and hepatocellular carcinoma (HCC) in the United States. We examine the effect of a universal newborn immunization with hepatitis B vaccine and mass population screening immunization program initiated in 1984 on rates of HBV and HCC in children 25 years later. During this time period, the population of Alaska Native people grew from an estimated 75,000 to 130,000 persons. A surveillance system to detect acute HBV infection in Alaska Native facilities was established in 1981. Cases of HCC in children under 20 years of age were identified using a National Cancer Institute (NCI) funded Cancer Registry established in 1969 coupled with an active surveillance program of screening persons with chronic HBV semiannually for alpha-fetoprotein since 1982. The incidence of acute symptomatic HBV infection in persons < 20 years of age fell from cases 19/100,000 in 1981-1982 to 0/100,000 in 1993-94, respectively. No cases of acute HBV have occurred in children since 1992. The incidence of HCC in persons < 20 years decreased from 3/100,000 in 1984-1988 to zero in 1995-1999 and no cases have occurred since 1999. The number of identified HBsAg-positive children < 20 years in the Alaska Native Population declined from 657 in 1987 to two in 2008. Universal newborn vaccination coupled with mass screening and immunization of susceptible Alaska Native has eliminated HCC and acute symptomatic HBV infection among Alaska Native children and this approach is the best way to prevent HBV related disease in children. (HEPATOLOGY 2011.). |
Repeat revaccination with 23-valent pneumococcal polysaccharide vaccine among adults aged 55-74 years living in Alaska: no evidence of hyporesponsiveness
Hammitt LL , Bulkow LR , Singleton RJ , Nuorti JP , Hummel KB , Miernyk KM , Zanis C , Whaley M , Romero-Steiner S , Butler JC , Rudolph K , Hennessy TW . Vaccine 2011 29 (12) 2287-95 BACKGROUND: Older adults are at highest risk of invasive pneumococcal disease (IPD) and are recommended to receive vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23). Antibody concentrations decline following vaccination. We evaluated the immunogenicity and reactogenicity of revaccination and repeat revaccination. METHODS: Adults aged 55-74 years were vaccinated with a 1st to 4th dose of PPV23. Participants were eligible for revaccination if a minimum of 6 years had passed since their last dose of PPV23. Blood collected on the day of vaccination and 30 days later was analyzed by ELISA for IgG to five serotypes. Functional antibody activity was measured using an opsonophagocytic killing (OPK) assay. Reactions to vaccination were documented. RESULTS: Subjects were vaccinated with a 1st dose (n=123), 2nd dose (n=121), or 3rd or 4th dose (n=71) of PPV23. The post-vaccination IgG geometric mean concentrations (GMCs) were similar among first-time vaccinees and re-vaccinees for all serotypes with the exception of a lower GMC for serotype 1 in re-vaccinees. The post-vaccination OPK geometric mean titers (GMTs) were similar among first-time vaccinees and re-vaccinees with the exception of a higher GMT for serotype 6B in re-vaccinees. Compared to first-time vaccinees, re-vaccinees reported more joint pain (p=0.003), fatigue (p=0.027), headache (p=0.011), swelling (p=0.009), and moderate limitation in arm movement (p=0.015). CONCLUSIONS: Repeat revaccination with PPV23, administered 6 or more years after the prior dose, was immunogenic and generally well tolerated. |
Trends in hospitalization for empyema in Alaska native children yournger than 10 years of age
Singleton RJ , Holman RC , Wenger J , Christensen KY , Bulkow LR , Zulz T , Steiner CA , Cheek JE . Pediatr Infect Dis J 2010 30 (6) 528-30 We analyzed hospitalizations for empyema among Alaska Native (AN) children and the general population of US children <10 years during the years 1998 to 2007. We also analyzed invasive pneumococcal disease in AN children. Between 1998 and 2000, the average annual hospitalization rate for empyema was higher for AN children (51.8 per 100,000/yr) than that for US children (24.2 [95% confidence interval: 20.4, 27.9] per 100,000/yr), and had increased in 2004-2007 in both populations (59.6 and 36.0 [95% confidence interval: 30.1, 41.8], respectively). Pneumococcal empyema increased in AN children despite a decrease in invasive pneumococcal disease pneumonia. |
Long-term immunogenicity of inactivated hepatitis A vaccine: follow-up at 15 years
Byrd KK , Bruden DL , Bruce MG , Bulkow LR , Zanis CL , Snowball MM , Homan CE , Hennessy TW , Williams JL , Dunaway E , Chaves SS , McMahon BJ . J Pediatr Infect Dis 2010 5 (4) 321-326 We conducted a 10-15 years follow-up to a long-term prospective cohort study on the immunogenicity of inactivated hepatitis A vaccine in Alaska Native children, who were initially vaccinated between 3-6 years of age. Children received three vaccine doses (320 E.U.) and were randomized into the following vaccination schedules: A (0, 1, 2 months); B (0, 1, 6 months); and C (0, 1, 12 months). Sera were collected every 2 years and tested for hepatitis A virus (anti-HAV). Levels 20 mIU/mL were considered protective. Anti-HAV geometric mean concentrations were compared by vaccination schedule at 10, 12 and 14 years of follow-up, using ANOVA. Antibody decline over the entire 15-year follow-up period was also analyzed. While none of the inter-schedule comparisons differed significantly from each other at the 10, 12 and 14-year periods, schedules B and C had significantly higher anti-HAV levels than schedule A over the entire 15 years of the study (P0.01). All schedule B and C children maintained seroprotective levels in all follow-up periods. Fourteen percent of schedule A children fell below seroprotective levels at 14 years. Our model estimated that anti-HAV geometric mean concentrations would fall below seroprotective levels at 26, 30 and 32 years for schedules A, B and C, respectively. The data indicate that hepatitis A immunity lasts at least 15 years after vaccination in children and that a booster dose is not needed during that time. However, continued monitoring is necessary to assess the need for a booster dose later in the second and third decade after receipt of the primary series. |
Diabetes prevalence, incidence, complications and mortality among Alaska Native people 1985-2006
Narayanan ML , Schraer CD , Bulkow LR , Koller KR , Asay E , Mayer AM , Raymer TW . Int J Circumpolar Health 2010 69 (3) 236-52 OBJECTIVES: To examine trends in diabetes prevalence, incidence, complications and mortality between 1985 and 2006 among Alaska Native people. STUDY DESIGN: We used data from the population-based Alaska Native Diabetes Registry, which includes all people who receive care in the Alaska Tribal Health System. METHODS: We compared the periods of 1986-1990 and 2002-2006 for diabetes-related amputations, renal replacement and mortality using Poisson regression. Complications and mortality data were examined for trends using Poisson regression. Survival analyses for those diagnosed since 31 December 1985 were performed using the Cox proportional hazard model. RESULTS: Age-adjusted diabetes prevalence increased from 17.3 in 1985 to 47.6/1,000 in 2006. The number of Alaska Native people living in Alaska with diabetes increased from 610 in 1985 to 3,386 in 2006. Diabetes incidence rates have also increased. Comparing age-adjusted rates for the 5-year periods 1986-1990 and 2002-2006, amputations decreased from 5.3 to 2.6/1,000, renal replacement decreased from 3.3 to 1.2/1,000 and mortality decreased from 41.7 to 33.2/1,000. Yearly analyses showed a downward trend for amputations, renal replacement and mortality rates. Survival analyses showed a significantly higher hazard ratio for any amputations, major amputations and renal replacement for the earlier time period compared to the most recent time period. CONCLUSIONS: An increase in risk factors, awareness, funding and case-finding may be contributing to the increase in prevalence and incidence of diagnosed diabetes. While diabetes prevalence and incidence are increasing among Alaska Native people, our results suggest that even in remote, rural areas, complications and mortality can be reduced. |
Impact of a statewide childhood vaccine program in controlling hepatitis A virus infections in Alaska
Singleton RJ , Hess S , Bulkow LR , Castrodale L , Provo G , McMahon BJ . Vaccine 2010 28 (38) 6298-304 Historically, Alaska experienced cyclic hepatitis A virus (HAV) epidemics, and the HAV rate among Alaska Native people was significantly higher than among other racial/ethnic groups. We evaluated the impact of universal childhood vaccination, initiated in 1996, on HAV epidemiology in Alaska by analyzing HAV cases reported to the State of Alaska. HAV incidence in all age groups declined 98.6% from 60.0/100,000 in 1972-1995 to 0.9/100,000 in 2002-2007. The largest decrease (99.9%) was in Alaska Native people, whose incidence (0.3) in 2002-2007 was lower than the overall US 2007 rate (1.0). Among age groups, the decrease (99.8%) among children aged 0-14 years was the largest. Routine childhood vaccination has nearly eliminated HAV infection in Alaska. |
Viral respiratory infections in hospitalized and community control children in Alaska
Singleton RJ , Bulkow LR , Miernyk K , DeByle C , Pruitt L , Hummel KB , Bruden D , Englund JA , Anderson LJ , Lucher L , Holman RC , Hennessy TW . J Med Virol 2010 82 (7) 1282-90 Respiratory syncytial virus (RSV) in Alaska Native children from the Yukon Kuskokwim (YK) Delta is associated with a hospitalization rate five times higher than that reported for the general US child population. The role of other viral respiratory pathogens has not been studied in this population. YK Delta children <3 years of age hospitalized with respiratory infections and same aged community control children were prospectively enrolled between October 2005 and September 2007. Polymerase chain reaction detection of viruses was performed on nasopharyngeal samples. Characteristics of hospitalized and asymptomatic control children were analyzed. From October 2005 to September 2007, 440 hospitalized and 425 control children were analyzed. Respiratory viruses were detected in 90% (395) of hospitalized children: 194 (44%) rhinovirus, 131 (30%) adenovirus, 102 (23%) RSV, 77 (18%) para influenza viruses (PIV), 66 (15%) human metapneumovirus (hMPV), 23 (5%) influenza, and 25 (6%) coronavirus. Fifty-two percent (221) of control children had a virus detected, most commonly rhinovirus (33%), and adenovirus (16%). RSV, PIV, hMPV, and influenza were significantly more common in hospitalized cases than control children, but rhinovirus, adenovirus, and coronavirus were not. RSV and hMPV were associated with higher severity of illness. In this study, RSV remains the most important virus associated with respiratory hospitalization, although hMPV and PIV were also common. RSV and hMPV were associated with more severe illness. Rhinovirus and adenovirus were detected in two-thirds of hospitalized children, but their frequent detection in control children made their role in respiratory hospitalization uncertain. |
Immunogenicity and reactogenicity of pneumococcal polysaccharide and conjugate vaccines in Alaska native adults 55-70 years of age
Miernyk KM , Butler JC , Bulkow LR , Singleton RJ , Hennessy TW , Dentinger CM , Peters HV , Knutsen B , Hickel J , Parkinson AJ . Clin Infect Dis 2009 49 (2) 241-8 BACKGROUND: Vaccination with conjugate vaccines stimulates T cell-dependent immunity, whereas vaccination with polysaccharide vaccines does not. Thus, vaccination with the 7-valent pneumococcal conjugate vaccine (PCV7) followed by the 23-valent pneumococcal polysaccharide vaccine (PPV23) may offer better protection against invasive pneumococcal disease for older adults than does vaccination with PPV23 alone, which is what is currently recommended. METHODS: Alaska Native adults 55-70 years of age with no previous pneumococcal vaccination were randomized to receive (1) PPV23, (2) PCV7 followed 2 months later by PPV23, or (3) PCV7 followed 6 months later by PPV23. Participants recorded reactions after each vaccination. Serum samples collected during the period from May 2002 through February 2003 were tested for serotype-specific immunoglobulin G (IgG) and for opsonophagocytic activity (OPA) against serotypes 1, 4, 6B, 14, and 19F. RESULTS: Vaccination with PCV7 was well tolerated, but persons receiving PCV7 followed by PPV23 reported more local reactions than those receiving only PPV23. All reactions resolved spontaneously within 72 h of receiving vaccine. The geometric mean IgG concentrations of and the median OPA titers to serotypes 4, 6B, 14, and 19F increased in all groups after 1 dose of either PCV7 or PPV23. Serotype-specific geometric mean IgG concentrations and median OPA titers did not differ between any of the groups after vaccination with PPV23, regardless of whether they had previously received PCV7. CONCLUSIONS: In this study, PCV7 given 2 or 6 months before PPV23 was well tolerated but did not improve immune response to PPV23 in older Alaska Native adults. |
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