Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-14 (of 14 Records) |
Query Trace: Harker E[original query] |
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Serotype distribution of remaining invasive pneumococcal disease after extensive use of ten-valent and 13-valent pneumococcal conjugate vaccines (the PSERENADE project): a global surveillance analysis
Garcia Quesada M , Peterson ME , Bennett JC , Hayford K , Zeger SL , Yang Y , Hetrich MK , Feikin DR , Cohen AL , von Gottberg A , van der Linden M , van Sorge NM , de Oliveira LH , de Miguel S , Yildirim I , Vestrheim DF , Verani JR , Varon E , Valentiner-Branth P , Tzanakaki G , Sinkovec Zorko N , Setchanova LP , Serhan F , Scott KJ , Scott JA , Savulescu C , Savrasova L , Reyburn R , Oishi K , Nuorti JP , Napoli D , Mwenda JM , Muñoz-Almagro C , Morfeldt E , McMahon K , McGeer A , Mad'arová L , Mackenzie GA , Eugenia León M , Ladhani SN , Kristinsson KG , Kozakova J , Kleynhans J , Klein NP , Kellner JD , Jayasinghe S , Ho PL , Hilty M , Harker-Jones MA , Hammitt LL , Grgic-Vitek M , Gilkison C , Gierke R , French N , Diawara I , Desmet S , De Wals P , Dalby T , Dagan R , Corcoran M , Colzani E , Chanto Chacón G , Castilla J , Camilli R , Ang M , Ampofo K , Almeida SCG , Alarcon P , O'Brien KL , Deloria Knoll M . Lancet Infect Dis 2024 ![]() BACKGROUND: Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally. METHODS: IPD data were obtained from surveillance sites participating in the WHO-commissioned Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project that exclusively used PCV10 or PCV13 (hereafter PCV10 and PCV13 sites, respectively) in their national immunisation programmes and had primary series uptake of at least 70%. Serotype distribution was estimated for IPD cases occurring 5 years or more after PCV10 or PCV13 introduction (ie, the mature period when the serotype distribution had stabilised) using multinomial Dirichlet regression, stratified by PCV product and age group (<5 years, 5-17 years, 18-49 years, and ≥50 years). FINDINGS: The analysis included cases occurring primarily between 2015 and 2018 from 42 PCV13 sites (63 362 cases) and 12 PCV10 sites (6806 cases) in 41 countries. Sites were mostly high income (36 [67%] of 54) and used three-dose or four-dose booster schedules (44 [81%]). At PCV10 sites, PCV10 serotypes caused 10·0% (95% CI 6·3-12·9) of IPD cases in children younger than 5 years and 15·5% (13·4-19·3) of cases in adults aged 50 years or older, while PCV13 serotypes caused 52·1% (49·2-65·4) and 45·6% (40·0-50·0), respectively. At PCV13 sites, PCV13 serotypes caused 26·4% (21·3-30·0) of IPD cases in children younger than 5 years and 29·5% (27·5-33·0) of cases in adults aged 50 years or older. The leading serotype at PCV10 sites was 19A in children younger than 5 years (30·6% [95% CI 18·2-43·1]) and adults aged 50 years or older (14·8% [11·9-17·8]). Serotype 3 was a top-ranked serotype, causing about 9% of cases in children younger than 5 years and 14% in adults aged 50 years or older at both PCV10 and PCV13 sites. Across all age and PCV10 or PCV13 strata, the proportion of IPD targeted by higher-valency PCVs beyond PCV13 was 4·1-9·7% for PCV15, 13·5-36·0% for PCV20, 29·9-53·8% for PCV21, 15·6-42·0% for PCV24, and 31·5-50·1% for PCV25. All top-ten ranked non-PCV13 serotypes are included in at least one higher-valency PCV. INTERPRETATION: The proportion of IPD due to serotypes included in PCVs in use was low in mature PCV10 and PCV13 settings. Serotype distribution differed between PCV10 and PCV13 sites and age groups. Higher-valency PCVs target most remaining IPD and are expected to extend impact. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project. |
Benefit of early oseltamivir therapy for adults hospitalized with influenza A: an observational study
Lewis NM , Harker EJ , Grant LB , Zhu Y , Grijalva CG , Chappell JD , Rhoads JP , Baughman A , Casey JD , Blair PW , Jones ID , Johnson CA , Lauring AS , Gaglani M , Ghamande S , Columbus C , Steingrub JS , Shapiro NI , Duggal A , Busse LW , Felzer J , Prekker ME , Peltan ID , Brown SM , Hager DN , Gong MN , Mohamed A , Exline MC , Khan A , Hough CL , Wilson JG , Mosier J , Qadir N , Chang SY , Ginde AA , Martinez A , Mohr NM , Mallow C , Harris ES , Johnson NJ , Srinivasan V , Gibbs KW , Kwon JH , Vaughn IA , Ramesh M , Safdar B , Goyal A , DeLamielleure LE , DeCuir J , Surie D , Dawood FS , Tenforde MW , Uyeki TM , Garg S , Ellington S , Self WH . Clin Infect Dis 2024 BACKGROUND: clinical guidelines recommend initiation of antiviral therapy as soon as possible for patients hospitalized with confirmed or suspected influenza. METHODS: A multicenter US observational sentinel surveillance network prospectively enrolled adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza at 24 hospitals during October 1, 2022-July 21, 2023. A multivariable proportional odds model was used to compare peak pulmonary disease severity (no oxygen support, standard supplemental oxygen, high-flow oxygen/non-invasive ventilation, invasive mechanical ventilation, or death) after the day of hospital admission among patients starting oseltamivir treatment on the day of admission (early) versus those who did not (late or not treated), adjusting for baseline (admission day) severity, age, sex, site, and vaccination status. Multivariable logistic regression models were used to evaluate the odds of intensive care unit (ICU) admission, acute kidney replacement therapy or vasopressor use, and in-hospital death. RESULTS: A total of 840 influenza-positive patients were analyzed, including 415 (49%) who started oseltamivir treatment on the day of admission, and 425 (51%) who did not. Compared with late or not treated patients, those treated early had lower peak pulmonary disease severity (proportional aOR: 0.60, 95% CI: 0.49-0.72), and lower odds of intensive care unit admission (aOR: 0.24, 95% CI: 0.13-0.47), acute kidney replacement therapy or vasopressor use (aOR: 0.40, 95% CI: 0.22-0.67), and in-hospital death (aOR: 0.36, 95% CI: 0.18-0.72). CONCLUSION: Among adults hospitalized with influenza, treatment with oseltamivir on day of hospital admission was associated reduced risk of disease progression, including pulmonary and extrapulmonary organ failure and death. |
Assessment and mitigation of bias in influenza and COVID-19 vaccine effectiveness analyses - IVY Network, September 1, 2022-March 30, 2023
Lewis NM , Harker EJ , Leis A , Zhu Y , Talbot HK , Grijalva CG , Halasa N , Chappell JD , Johnson CA , Rice TW , Casey JD , Lauring AS , Gaglani M , Ghamande S , Columbus C , Steingrub JS , Shapiro NI , Duggal A , Felzer J , Prekker ME , Peltan ID , Brown SM , Hager DN , Gong MN , Mohamed A , Exline MC , Khan A , Wilson JG , Mosier J , Qadir N , Chang SY , Ginde AA , Mohr NM , Mallow C , Harris ES , Johnson NJ , Srinivasan V , Gibbs KW , Kwon JH , Vaughn IA , Ramesh M , Safdar B , DeCuir J , Surie D , Dawood FS , Ellington S , Self WH , Martin ET . Vaccine 2024 43 126492 BACKGROUND: In test-negative studies of vaccine effectiveness (VE), including patients with co-circulating, vaccine-preventable, respiratory pathogens in the control group for the pathogen of interest can introduce a downward bias on VE estimates. METHODS: A multicenter sentinel surveillance network in the US prospectively enrolled adults hospitalized with acute respiratory illness from September 1, 2022-March 31, 2023. We evaluated bias in estimates of VE against influenza-associated and COVID-19-associated hospitalization based on: inclusion vs exclusion of patients with a co-circulating virus among VE controls; observance of VE against the co-circulating virus (rather than the virus of interest), unadjusted and adjusted for vaccination against the virus of interest; and observance of influenza or COVID-19 against a sham outcome of respiratory syncytial virus (RSV). RESULTS: Overall VE against influenza-associated hospitalizations was 6 percentage points lower when patients with COVID-19 were included in the control group, and overall VE against COVID-19-associated hospitalizations was 2 percentage points lower when patients with influenza were included in the control group. Analyses of VE against the co-circulating virus and against the sham outcome of RSV showed that downward bias was largely attributable the correlation of vaccination status across pathogens, but also potentially attributable to other sources of residual confounding in VE models. CONCLUSION: Excluding cases of confounding respiratory pathogens from the control group in VE analysis for a pathogen of interest can reduce downward bias. This real-world analysis demonstrates that such exclusion is a helpful bias mitigation strategy, especially for measuring influenza VE, which included a high proportion of COVID-19 cases among controls. |
Streptococcus pneumoniae serotype 3 population structure in the era of conjugate vaccines, 2001-2018
Cella E , Sutcliffe CG , Grant LR , Tso C , Weatherholtz RC , Littlepage S , Becenti L , Jubair M , Simons BC , Harker-Jones M , Reid R , Yazzie D , Santosham M , O'Brien KL , Hammitt LL , Azarian T . Microb Genom 2024 10 (3) ![]() ![]() Background. Despite use of highly effective conjugate vaccines, invasive pneumococcal disease (IPD) remains a leading cause of morbidity and mortality and disproportionately affects Indigenous populations. Although included in the 13-valent pneumococcal conjugate vaccine (PCV13), which was introduced in 2010, serotype 3 continues to cause disease among Indigenous communities in the Southwest USA. In the Navajo Nation, serotype 3 IPD incidence increased among adults (3.8/100 000 in 2001-2009 and 6.2/100 000 in 2011-2019); in children the disease persisted although the rates dropped from 5.8/100 000 to 2.3/100 000.Methods. We analysed the genomic epidemiology of serotype 3 isolates collected from 129 adults and 63 children with pneumococcal carriage (n=61) or IPD (n=131) from 2001 to 2018 of the Navajo Nation. Using whole-genome sequencing data, we determined clade membership and assessed changes in serotype 3 population structure over time.Results. The serotype 3 population structure was characterized by three dominant subpopulations: clade II (n=90, 46.9 %) and clade Iα (n=59, 30.7 %), which fall into Clonal Complex (CC) 180, and a non-CC180 clade (n=43, 22.4 %). The proportion of clade II-associated IPD cases increased significantly from 2001 to 2010 to 2011-2018 among adults (23.1-71.8 %; P<0.001) but not in children (27.3-33.3 %; P=0.84). Over the same period, the proportion of clade II-associated carriage increased; this was statistically significant among children (23.3-52.6 %; P=0.04) but not adults (0-50.0 %, P=0.08).Conclusions. In this setting with persistent serotype 3 IPD and carriage, clade II has increased since 2010. Genomic changes may be contributing to the observed trends in serotype 3 carriage and disease over time. |
Interim estimates of 2023-24 seasonal influenza vaccine effectiveness - United States
Frutos AM , Price AM , Harker E , Reeves EL , Ahmad HM , Murugan V , Martin ET , House S , Saade EA , Zimmerman RK , Gaglani M , Wernli KJ , Walter EB , Michaels MG , Staat MA , Weinberg GA , Selvarangan R , Boom JA , Klein EJ , Halasa NB , Ginde AA , Gibbs KW , Zhu Y , Self WH , Tartof SY , Klein NP , Dascomb K , DeSilva MB , Weber ZA , Yang DH , Ball SW , Surie D , DeCuir J , Dawood FS , Moline HL , Toepfer AP , Clopper BR , Link-Gelles R , Payne AB , Chung JR , Flannery B , Lewis NM , Olson SM , Adams K , Tenforde MW , Garg S , Grohskopf LA , Reed C , Ellington S . MMWR Morb Mortal Wkly Rep 2024 73 (8) 168-174 In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally. |
Vaccine effectiveness against influenza a-associated hospitalization, organ failure, and death: United States, 2022-2023
Lewis NM , Zhu Y , Peltan ID , Gaglani M , McNeal T , Ghamande S , Steingrub JS , Shapiro NI , Duggal A , Bender WS , Taghizadeh L , Brown SM , Hager DN , Gong MN , Mohamed A , Exline MC , Khan A , Wilson JG , Qadir N , Chang SY , Ginde AA , Mohr NM , Mallow C , Lauring AS , Johnson NJ , Gibbs KW , Kwon JH , Columbus C , Gottlieb RL , Raver C , Vaughn IA , Ramesh M , Johnson C , Lamerato L , Safdar B , Casey JD , Rice TW , Halasa N , Chappell JD , Grijalva CG , Talbot HK , Baughman A , Womack KN , Swan SA , Harker E , Price A , DeCuir J , Surie D , Ellington S , Self WH . Clin Infect Dis 2023 BACKGROUND: Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain. METHODS: To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative control-patients. RESULTS: A total of 3707 patients, including 714 influenza cases (33% vaccinated) and 2993 influenza- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls (49% vaccinated) were analyzed. VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%-46%) and varied by age (18-64 years: 47% [30%-60%]; ≥65 years: 28% [10%-43%]), and virus (A[H3N2]: 29% [6%-46%], A[H1N1]: 47% [23%-64%]). VE against more severe influenza-associated outcomes included: 41% (29%-50%) against influenza with hypoxemia treated with supplemental oxygen; 65% (56%-72%) against influenza with respiratory, cardiovascular, or renal failure treated with organ support; and 66% (40%-81%) against influenza with respiratory failure treated with invasive mechanical ventilation. CONCLUSIONS: During an early 2022-2023 influenza season with a well-matched influenza vaccine, vaccination was associated with reduced risk of influenza-associated hospitalization and organ failure. |
SARS-CoV-2 epidemiology and COVID-19 mRNA vaccine effectiveness among infants and children aged 6 months-4 years - New Vaccine Surveillance Network, United States, July 2022-September 2023
Tannis A , Englund JA , Perez A , Harker EJ , Staat MA , Schlaudecker EP , Halasa NB , Stewart LS , Williams JV , Michaels MG , Selvarangan R , Schuster JE , Sahni LC , Boom JA , Weinberg GA , Szilagyi PG , Clopper BR , Zhou Y , McMorrow ML , Klein EJ , Moline HL . MMWR Morb Mortal Wkly Rep 2023 72 (48) 1300-1306 ![]() ![]() SARS-CoV-2 infection in young children is often mild or asymptomatic; however, some children are at risk for severe disease. Data describing the protective effectiveness of COVID-19 mRNA vaccines against COVID-19-associated emergency department (ED) visits and hospitalization in this population are limited. Data from the New Vaccine Surveillance Network, a prospective population-based surveillance system, were used to estimate vaccine effectiveness using a test-negative, case-control design and describe the epidemiology of SARS-CoV-2 in infants and children aged 6 months-4 years during July 1, 2022-September 30, 2023. Among 7,434 children included, 5% received a positive SARS-CoV-2 test result, and 95% received a negative test result; 86% were unvaccinated, 4% had received 1 dose of any vaccine product, and 10% had received ≥2 doses. When compared with receipt of no vaccines among children, receipt of ≥2 COVID-19 mRNA vaccine doses was 40% effective (95% CI = 8%-60%) in preventing ED visits and hospitalization. These findings support existing recommendations for COVID-19 vaccination of young children to reduce COVID-19-associated ED visits and hospitalization. |
Respiratory Virus Surveillance Among Children with Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021.
Perez A , Lively JY , Curns A , Weinberg GA , Halasa NB , Staat MA , Szilagyi PG , Stewart LS , McNeal MM , Clopper B , Zhou Y , Whitaker BL , LeMasters E , Harker E , Englund JA , Klein EJ , Selvarangan R , Harrison CJ , Boom JA , Sahni LC , Michaels MG , Williams JV , Langley GE , Gerber SI , Campbell A , Hall AJ , Rha B , McMorrow M . MMWR Morb Mortal Wkly Rep 2022 71 (40) 1253-1259 The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN inpatient (i.e., hospital) surveillance began in 2015, expanded to emergency departments (EDs) in 2016, and to outpatient clinics in 2018. This report describes demographic characteristics of enrolled children who received care in these settings, and yearly circulation of influenza, RSV, HMPV, HPIV1-3, adenovirus, human rhinovirus and enterovirus (RV/EV),* and SARS-CoV-2 during December 2016-August 2021. Among 90,085 eligible infants, children, and adolescents (children) aged <18 years(†) with ARI, 51,441 (57%) were enrolled, nearly 75% of whom were aged <5 years; 43% were hospitalized. Infants aged <1 year accounted for the largest proportion (38%) of those hospitalized. The most common pathogens detected were RV/EV and RSV. Before the emergence of SARS-CoV-2, detected respiratory viruses followed previously described seasonal trends, with annual peaks of influenza and RSV in late fall and winter (7,8). After the emergence of SARS-CoV-2 and implementation of associated pandemic nonpharmaceutical interventions and community mitigation measures, many respiratory viruses circulated at lower-than-expected levels during April 2020-May 2021. Beginning in summer 2021, NVSN detected higher than anticipated enrollment of hospitalized children as well as atypical interseasonal circulation of RSV. Further analyses of NVSN data and continued surveillance are vital in highlighting risk factors for severe disease and health disparities, measuring the effectiveness of vaccines and monoclonal antibody-based prophylactics, and guiding policies to protect young children from pathogens such as SARS-CoV-2, influenza, and RSV. |
Predicting adolescent boys' and young men's perpetration of youth violence in Colombia
Seff I , Meinhart M , Harker Roa A , Stark L , Villaveces A . Int J Inj Contr Saf Promot 2021 29 (1) 1-9 Youth violence poses a substantive public health burden in Latin America, particularly among adolescent boys and young men. Understanding predictors of youth violence perpetration among boys and young men is critical to more effectively target and tailor prevention programs, especially in Colombia, which has endured decades-long internal armed conflict. This study uses Colombia's nationally representative 2018 Violence Against Children and Youth Survey data to examine risk and protective factors associated with violence perpetration among 13- to 24-year-old male. Amongst adolescent boys and young men in Colombia, the prevalence of ever perpetrating violence against someone other than an intimate partner was approximately 23%. Multivariable logistic regression models revealed that physical violence victimization by peers, emotional violence victimization by caregivers, having lost or been separated from a mother during childhood, and witnessing community violence were all associated with lifetime perpetration of youth violence. Programs targeting reduction of youth violence among boys might consider addressing the previously identified predictors earlier in the life course and at the individual, family and community levels. |
Human prion disease surveillance in Washington state, 2006-2017
Sánchez-González L , Maddox RA , Lewis LC , Blevins JE , Harker EJ , Appleby BS , Person MK , Schonberger LB , Belay ED , DeBolt C , Lofy KH . JAMA Netw Open 2020 3 (10) e2020690 IMPORTANCE: Human prion disease surveillance is critical to detect possible cases of variant Creutzfeldt-Jakob disease and other acquired forms of prion disease in the United States. Results are presented here that describe 12 years of surveillance in Washington, the only US state that has reported the presence of classic bovine spongiform encephalopathy, an animal prion disease that has been shown to transmit to humans. OBJECTIVE: To describe the current prion disease surveillance system in Washington and the epidemiological and clinical results of surveillance from 2006 through 2017. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study reports findings from the human prion disease surveillance system in place in Washington state from January 1, 2006, through December 31, 2017. Participants included Washington residents with a clinical suspicion of human prion disease or suggestive test results from the National Prion Disease Pathology Surveillance Center or with prion disease listed as a cause of death on the death certificate. Data for this report were analyzed from June 1, 2016, to July 1, 2020. EXPOSURE: Human prion disease diagnosis. MAIN OUTCOMES AND MEASURES: The main outcome was incidence of human prion disease cases, including identification of variant Creutzfeldt-Jakob disease. RESULTS: A total of 143 human prion disease cases were detected during the study period, none of which met criteria for a variant Creutzfeldt-Jakob disease diagnosis. Among 137 definite or probable cases, 123 (89.8%) occurred in persons aged 55 years or older, with a median age at death of 66 years (range, 38-84 years). Most patients were White (124 [92.5%] among 134 with reported race), and slightly over half were male (70 [51.1%]). The average annual age-adjusted prion disease incidence was 1.5 per million population per year, slightly higher than the national rate of 1.2 per million. A total of 99 cases (69.2%) were confirmed by neuropathology. Sporadic prion disease was the most common diagnosis, in 134 cases (93.7%), followed by familial prion disease in 8 cases (5.6%). One iatrogenic prion disease case (0.7%) was also reported. CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that demographic characteristics of patients with prion disease in Washington are consistent with national findings. The slightly higher incidence rate may be due to the state's enhanced surveillance activities, including close collaboration with key partners and educational efforts targeted toward health care providers. Results indicate that surveillance will continue to be beneficial for monitoring epidemiological trends, facilitating accurate diagnoses, and detecting variant Creutzfeldt-Jakob disease or other emerging human prion disease cases. |
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). |
Molecular resistance mechanisms of macrolide-resistant invasive Streptococcus pneumoniae isolates from Alaska, 1986 to 2010.
Rudolph K , Bulkow L , Bruce M , Zulz T , Reasonover A , Harker-Jones M , Hurlburt D , Hennessy T . Antimicrob Agents Chemother 2013 57 (11) 5415-22 ![]() 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. |
Epidemiology of pneumococcal serotype 6A and 6C among invasive and carriage isolates from Alaska, 1986-2009.
Rudolph K , Bruce M , Bruden D , Zulz T , Wenger J , Reasonover A , Harker-Jones M , Hurlburt D , Hennessy T . Diagn Microbiol Infect Dis 2012 75 (3) 271-6 ![]() 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. |
Serotyping of Streptococcus pneumoniae isolates from nasopharyngeal samples: use of an algorithm combining microbiologic, serologic, and sequential multiplex PCR techniques.
Miernyk K , Debyle C , Harker-Jones M , Hummel KB , Hennessy T , Wenger J , Rudolph K . J Clin Microbiol 2011 49 (9) 3209-14 ![]() We evaluated nasopharyngeal carriage of Streptococcus pneumoniae (pneumococci) in nine Alaskan communities and used an algorithm combining microbiologic, serologic, and sequential multiplex PCR (MP-PCR) techniques to serotype the isolates. After microbiological identification as pneumococci, isolates (n = 1,135) were serotyped using latex agglutination and Quellung tests (LA/Q) as well as a series of six sequential MP-PCR assays. Results from the two methods agreed for 94% (1,064/1,135) of samples. Eighty-six percent (61/71) of the discordant results were resolved. Discordant results occurred because (i) the MP-PCR gel was misread (31/61 [51%]), (ii) the LA/Q agglutination was misinterpreted (13/61 [21%]), (iii) two serotypes or sets of serotypes were identified by MP-PCR and only one of the two was identified by LA/Q (9/61 [15%]), (iv) different serotypes or sets of serotypes were identified by LA/Q and MP-PCR and both were correct (7/61 [11%]), and (v) the capsular polysaccharide locus (cps) did not amplify during the initial MP-PCR but was present upon retesting (1/61 [2%]). Overall, isolation of pneumococci followed by MP-PCR quickly and accurately identified pneumococcal serotypes in >97% of samples and made available isolates for additional tests such as antimicrobial susceptibility. Misinterpretation of the MP-PCR gel was identified as the main source of discordance. Increasing the number of MP-PCRs from six to seven and reducing the number of serotypes in each reaction may reduce this error. This method may be of use to laboratories characterizing large numbers of S. pneumoniae samples, especially when antimicrobial susceptibility data are needed. |
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