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Neal EFG, Chan J, Nguyen CD, Russell FM. Factors associated with pneumococcal nasopharyngeal carriage: A systematic review. PLOS GLOBAL PUBLIC HEALTH 2022; 2:e0000327. [PMID: 36962225 PMCID: PMC10021834 DOI: 10.1371/journal.pgph.0000327] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 03/14/2022] [Indexed: 11/19/2022]
Abstract
Pneumococcal disease is a major contributor to global childhood morbidity and mortality and is more common in low- and middle-income countries (LMICs) than in high-income countries. Pneumococcal carriage is a prerequisite for pneumococcal disease. Pneumococcal conjugate vaccine reduces vaccine-type carriage and disease. However, pneumococcal carriage and disease persist, and it is important to identify other potentially modifiable factors associated with pneumococcal carriage and determine if risk factors differ between low, middle, and high-income countries. This information may help inform pneumococcal disease prevention programs. This systematic literature review describes factors associated with pneumococcal carriage stratified by country income status and summarises pneumococcal carriage rates for included studies. We undertook a systematic search of English-language pneumococcal nasopharyngeal carriage studies up to 30th June 2021. Peer-reviewed studies reporting factors associated with overall pneumococcal nasopharyngeal carriage in healthy, community-based study populations were eligible for inclusion. Two researchers independently reviewed studies to determine eligibility. Results are presented as narrative summaries. This review is registered with PROSPERO, CRD42020186914. Eighty-two studies were included, and 46 (56%) were conducted in LMICs. There was heterogeneity in the factors assessed in each study. Factors positively associated with pneumococcal carriage in all income classification were young age, ethnicity, symptoms of respiratory tract infection, childcare attendance, living with young children, poverty, exposure to smoke, season, and co-colonisation with other pathogens. Breastfeeding and antibiotic use were protective against carriage in all income classifications. Median (interquartile range) pneumococcal carriage rates differed by income classification, ranging from 51% (19.3-70.2%), 38.5% (19.3-51.6%), 31.5% (19.0-51.0%), 28.5% (16.8-35.4%), (P = 0.005) in low-, lower-middle, upper-middle, and high-income classifications, respectively. Our findings suggest that where measured, factors associated with pneumococcal nasopharyngeal carriage are similar across income classifications, despite the highest pneumococcal carriage rates being in low-income classifications. Reducing viral transmission through vaccination and public health interventions to address social determinants of health would play an important role.
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Affiliation(s)
- Eleanor Frances Georgina Neal
- Infection & Immunity, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia
- Department of Paediatrics, The University of Melbourne, Parkville, Australia
| | - Jocelyn Chan
- Infection & Immunity, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia
- Department of Paediatrics, The University of Melbourne, Parkville, Australia
| | - Cattram Duong Nguyen
- Infection & Immunity, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia
- Department of Paediatrics, The University of Melbourne, Parkville, Australia
| | - Fiona Mary Russell
- Infection & Immunity, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia
- Department of Paediatrics, The University of Melbourne, Parkville, Australia
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2
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Ansari S, Hays JP, Kemp A, Okechukwu R, Murugaiyan J, Ekwanzala MD, Ruiz Alvarez MJ, Paul-Satyaseela M, Iwu CD, Balleste-Delpierre C, Septimus E, Mugisha L, Fadare J, Chaudhuri S, Chibabhai V, Wadanamby JMRWW, Daoud Z, Xiao Y, Parkunan T, Khalaf Y, M’Ikanatha NM, van Dongen MBM. The potential impact of the COVID-19 pandemic on global antimicrobial and biocide resistance: an AMR Insights global perspective. JAC Antimicrob Resist 2021; 3:dlab038. [PMID: 34192258 PMCID: PMC8083476 DOI: 10.1093/jacamr/dlab038] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The COVID-19 pandemic presents a serious public health challenge in all countries. However, repercussions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on future global health are still being investigated, including the pandemic's potential effect on the emergence and spread of global antimicrobial resistance (AMR). Critically ill COVID-19 patients may develop severe complications, which may predispose patients to infection with nosocomial bacterial and/or fungal pathogens, requiring the extensive use of antibiotics. However, antibiotics may also be inappropriately used in milder cases of COVID-19 infection. Further, concerns such as increased biocide use, antimicrobial stewardship/infection control, AMR awareness, the need for diagnostics (including rapid and point-of-care diagnostics) and the usefulness of vaccination could all be components shaping the influence of the COVID-19 pandemic. In this publication, the authors present a brief overview of the COVID-19 pandemic and associated issues that could influence the pandemic's effect on global AMR.
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Affiliation(s)
- Shamshul Ansari
- Department of Microbiology, Chitwan Medical College and Teaching Hospital, Bharatpur, 44200 Chitwan, Nepal
| | - John P Hays
- Department of Medical Microbiology & Infectious Diseases, Erasmus University Medical Centre Rotterdam (Erasmus MC), Rotterdam, The Netherlands
| | - Andrew Kemp
- Scientific Advisory Board of the British Institute of Cleaning Sciences, Northampton, UK
| | - Raymond Okechukwu
- Department of Clinical Pharmacy and Pharmacy Management, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Agulu Campus, Nigeria
| | | | - Mutshiene Deogratias Ekwanzala
- Department of Environmental, Water and Earth Sciences, Tshwane University of Technology, Pretoria, South Africa
- Environmental Engineering, Department of Civil Engineering, Kyung Hee University, Yongin-si, Gyeonggi-do, Republic of Korea
| | | | | | - Chidozie Declan Iwu
- School of Health Systems and Public Health, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | | | - Ed Septimus
- Department of Population Medicine, Harvard Medical School & Harvard Pilgrim Health Care Institute, Boston, MA, 02215, Texas A&M College of Medicine, Houston, TX 77030, USA
| | - Lawrence Mugisha
- College of Veterinary Medicine, Animal Resources & Biosecurity (COVAB), Makerere University, Kampala, Uganda
| | - Joseph Fadare
- Department of Pharmacology and Therapeutics, College of Medicine, Ekiti State University, Ado-Ekiti, Nigeria
| | - Susmita Chaudhuri
- Translational Health Science and Technology Institute, Faridabad 121001, India
| | - Vindana Chibabhai
- Department of Clinical Microbiology and Infectious Diseases, University of the Witwatersrand, and Clinical Microbiology Laboratory, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Johannesburg, South Africa
| | - J M Rohini W W Wadanamby
- Department of Microbiology, Lanka Hospital Diagnostics, Lanka Hospital 578, Elvitigala Mw, Colombo 05, Sri Lanka
| | - Ziad Daoud
- Department of Clinical Microbiology & Infection Prevention, Michigan Health Clinics-Saginaw, MI, USA and Department of Foundational Sciences, CMED-CMU, Mount Pleasant, MI, USA
| | - Yonghong Xiao
- State Key Laboratory for Diagnosis & Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 300013, China
| | - Thulasiraman Parkunan
- Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary and Animal Sciences, Institute of Agricultural Sciences, Rajiv Gandhi South Campus, Banaras Hindu University, Mirzapur, Uttar Pradesh, India
| | - Yara Khalaf
- Department of Epidemiology, High Institute of Public Health, Alexandria University, Alexandria, Egypt
| | - Nkuchia M M’Ikanatha
- Division of Infectious Disease Epidemiology, Pennsylvania Department of Health, Harrisburg, PA, USA
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Lourenço J, Daon Y, Gori A, Obolski U. Pneumococcal Competition Modulates Antibiotic Resistance in the Pre-Vaccination Era: A Modelling Study. Vaccines (Basel) 2021; 9:265. [PMID: 33809706 PMCID: PMC8002235 DOI: 10.3390/vaccines9030265] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 03/06/2021] [Accepted: 03/09/2021] [Indexed: 11/30/2022] Open
Abstract
The ongoing emergence of antibiotic resistant strains and high frequencies of antibiotic resistance of Streptococcus pneumoniae poses a major public health challenge. How and which ecological and evolutionary mechanisms maintain the coexistence of antibiotic resistant and susceptible strains remains largely an open question. We developed an individual-based, stochastic model expanding on a previous pneumococci modelling framework. We explore how between- and within-host mechanisms of competition can sustain observed levels of resistance to antibiotics in the pre-vaccination era. Our framework considers that within-host competition for co-colonization between resistant and susceptible strains can arise via pre-existing immunity (immunological competition) or intrinsic fitness differences due to resistance costs (ecological competition). We find that beyond stochasticity, population structure or movement, competition at the within-host level can explain observed resistance frequencies. We compare our simulation results to pneumococcal antibiotic resistance data in the European region using approximate Bayesian computation. Our results demonstrate that ecological competition for co-colonization can explain the variation in co-existence of resistant and susceptible pneumococci observed in the pre-vaccination era. Furthermore, we show that within-host pneumococcal competition can facilitate the maintenance of resistance in the pre-vaccination era. Accounting for these competition-related components of pneumococcal dynamics can improve our understanding of drivers for the emergence and maintenance of antibiotic resistance in pneumococci.
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Affiliation(s)
- José Lourenço
- Department of Zoology, University of Oxford, Oxford OX1 3SZ, UK
| | - Yair Daon
- School of Public Health, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel;
- Porter School of the Environment and Earth Sciences, Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel
| | - Andrea Gori
- NIHR Global Health Research Unit on Mucosal Pathogens, Division of Infection and Immunity, University College London, London WC1E 6BT, UK;
| | - Uri Obolski
- School of Public Health, Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel;
- Porter School of the Environment and Earth Sciences, Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel
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Nahm MH, Brissac T, Kilian M, Vlach J, Orihuela CJ, Saad JS, Ganaie F. Pneumococci Can Become Virulent by Acquiring a New Capsule From Oral Streptococci. J Infect Dis 2020; 222:372-380. [PMID: 31605125 PMCID: PMC7457184 DOI: 10.1093/infdis/jiz456] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Accepted: 09/05/2019] [Indexed: 12/20/2022] Open
Abstract
Pneumococcal conjugate vaccines have been successful, but their use has increased infections by nonvaccine serotypes. Oral streptococci often harbor capsular polysaccharide (PS) synthesis loci (cps). Although this has not been observed in nature, if pneumococcus can replace its cps with oral streptococcal cps, it may increase its serotype repertoire. In the current study, we showed that oral Streptococcus strain SK95 and pneumococcal strain D39 both produce structurally identical capsular PS, and their genetic backgrounds influence the amount of capsule production and shielding from nonspecific killing. SK95 is avirulent in a well-established in vivo mouse model. When acapsular pneumococcus was transformed with SK95 cps, the transformant became virulent and killed all mice. Thus, cps from oral Streptococcus strains can make acapsular pneumococcus virulent, and interspecies cps transfer should be considered a potential mechanism of serotype replacement. Our findings, along with publications from the US Centers for Disease Control and Prevention, highlight potential limitations of the 2013 World Health Organization criterion for studying pneumococcal serotypes carried without isolating bacteria. We show that an oral streptococcal strain, SK95, and a pneumococcal strain, D39, both produce chemically identical capsular PS. We also show that transferring SK95 cps into noncapsulated, avirulent pneumococcus gave it the capacity for virulence in a mouse model.
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Affiliation(s)
- Moon H Nahm
- Department of Medicine, University of Alabama at Birmingham, Birmingham, USA
| | - Terry Brissac
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Mogens Kilian
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Jiri Vlach
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Carlos J Orihuela
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Jamil S Saad
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Feroze Ganaie
- Department of Medicine, University of Alabama at Birmingham, Birmingham, USA
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Plumb ID, Gounder PP, Bruden DJ, Bulkow LR, Rudolph KM, Singleton RJ, Hennessy TW, Bruce MG. Increasing non-susceptibility to antibiotics within carried pneumococcal serotypes — Alaska, 2008–2015. Vaccine 2020; 38:4273-4280. [DOI: 10.1016/j.vaccine.2020.04.048] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 04/15/2020] [Accepted: 04/20/2020] [Indexed: 10/24/2022]
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Kobayashi M, Bigogo G, Kim L, Mogeni OD, Conklin LM, Odoyo A, Odiembo H, Pimenta F, Ouma D, Harris AM, Odero K, Milucky JL, Ouma A, Aol G, Audi A, Onyango C, Cosmas L, Jagero G, Farrar JL, da Gloria Carvalho M, Whitney CG, Breiman RF, Lessa FC. Impact of 10-Valent Pneumococcal Conjugate Vaccine Introduction on Pneumococcal Carriage and Antibiotic Susceptibility Patterns Among Children Aged <5 Years and Adults With Human Immunodeficiency Virus Infection: Kenya, 2009-2013. Clin Infect Dis 2020; 70:814-826. [PMID: 30959526 PMCID: PMC6942635 DOI: 10.1093/cid/ciz285] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2018] [Accepted: 04/03/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Kenya introduced 10-valent pneumococcal conjugate vaccine (PCV10) among children <1 year in 2011 with catch-up vaccination among children 1-4 years in some areas. We assessed changes in pneumococcal carriage and antibiotic susceptibility patterns in children <5 years and adults. METHODS During 2009-2013, we performed annual cross-sectional pneumococcal carriage surveys in 2 sites: Kibera (children <5 years) and Lwak (children <5 years, adults). Only Lwak had catch-up vaccination. Nasopharyngeal and oropharyngeal (adults only) swabs underwent culture for pneumococci; isolates were serotyped. Antibiotic susceptibility testing was performed on isolates from 2009 and 2013; penicillin nonsusceptible pneumococci (PNSP) was defined as penicillin-intermediate or -resistant. Changes in pneumococcal carriage by age (<1 year, 1-4 years, adults), site, and human immunodeficiency virus (HIV) status (adults only) were calculated using modified Poisson regression, with 2009-2010 as baseline. RESULTS We enrolled 2962 children (2073 in Kibera, 889 in Lwak) and 2590 adults (2028 HIV+, 562 HIV-). In 2013, PCV10-type carriage was 10.3% (Lwak) to 14.6% (Kibera) in children <1 year and 13.8% (Lwak) to 18.7% (Kibera) in children 1-4 years. This represents reductions of 60% and 63% among children <1 year and 52% and 60% among children 1-4 years in Kibera and Lwak, respectively. In adults, PCV10-type carriage decreased from 12.9% to 2.8% (HIV+) and from 11.8% to 0.7% (HIV-). Approximately 80% of isolates were PNSP, both in 2009 and 2013. CONCLUSIONS PCV10-type carriage declined in children <5 years and adults post-PCV10 introduction. However, PCV10-type and PNSP carriage persisted in children regardless of catch-up vaccination.
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Affiliation(s)
- Miwako Kobayashi
- Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Godfrey Bigogo
- Centre for Global Health Research, Kenya Medical Research Institute, Kisumu
| | - Lindsay Kim
- Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia
- US Public Health Service, Rockville, Maryland
| | | | - Laura M Conklin
- Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Arthur Odoyo
- Centre for Global Health Research, Kenya Medical Research Institute, Kisumu
| | - Herine Odiembo
- Centre for Global Health Research, Kenya Medical Research Institute, Kisumu
| | - Fabiana Pimenta
- Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Dominic Ouma
- Centre for Global Health Research, Nairobi, Kenya
| | - Aaron M Harris
- Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia
| | | | - Jennifer L Milucky
- Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Alice Ouma
- Centre for Global Health Research, Nairobi, Kenya
| | - George Aol
- Centre for Global Health Research, Kenya Medical Research Institute, Kisumu
| | - Allan Audi
- Centre for Global Health Research, Kenya Medical Research Institute, Kisumu
| | - Clayton Onyango
- Global Disease Detection Division, Centers for Disease Control and Prevention, Nairobi
| | - Leonard Cosmas
- Global Disease Detection Division, Centers for Disease Control and Prevention, Nairobi
| | - Geofrey Jagero
- Centre for Global Health Research, Kenya Medical Research Institute, Kisumu
- University of Maryland School of Medicine, Center for International Health, Education, and Biosecurity Kenya Programs, Nairobi
| | - Jennifer L Farrar
- Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia
| | | | - Cynthia G Whitney
- Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Robert F Breiman
- Centre for Global Health Research, Nairobi, Kenya
- Emory Global Health Institute, Atlanta, Georgia
| | - Fernanda C Lessa
- Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia
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7
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Tin Tin Htar M, Sings HL, Syrochkina M, Taysi B, Hilton B, Schmitt HJ, Gessner BD, Jodar L. The impact of pneumococcal conjugate vaccines on serotype 19A nasopharyngeal carriage. Expert Rev Vaccines 2019; 18:1243-1270. [DOI: 10.1080/14760584.2019.1675521] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Affiliation(s)
| | - Heather L. Sings
- Vaccines Medical Development and Scientific and Clinical Affairs, Pfizer Inc, Collegeville, PA, USA
| | - Maria Syrochkina
- Vaccines Medical Development and Scientific and Clinical Affairs, Pfizer Inc, Moscow, Russia
| | - Bulent Taysi
- Vaccines Medical Development and Scientific and Clinical Affairs, Pfizer Inc, Istanbul, Turkey
| | - Betsy Hilton
- Vaccines Medical Development and Scientific and Clinical Affairs, Pfizer Inc, Collegeville, PA, USA
| | - Heinz-Josef Schmitt
- Vaccines Medical Development and Scientific and Clinical Affairs, Pfizer Inc, Collegeville, PA, USA
| | - Bradford D. Gessner
- Vaccines Medical Development and Scientific and Clinical Affairs, Pfizer Inc, Collegeville, PA, USA
| | - Luis Jodar
- Vaccines Medical Development and Scientific and Clinical Affairs, Pfizer Inc, Collegeville, PA, USA
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8
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Dagan R. Relationship between immune response to pneumococcal conjugate vaccines in infants and indirect protection after vaccine implementation. Expert Rev Vaccines 2019; 18:641-661. [PMID: 31230486 DOI: 10.1080/14760584.2019.1627207] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Introduction: Streptococcus pneumoniae is a leading cause of morbidity and mortality worldwide. Widespread infant vaccination with pneumococcal conjugate vaccines (PCVs) substantially reduced vaccine-serotype pneumococcal disease by direct protection of immunized children and indirect protection of the community via decreased nasopharyngeal carriage and transmission. Essential to grasping the public health implications of pediatric PCV immunization is an understanding of how PCV formulations impact carriage. Areas covered: Using clinical evidence, this review examines how the immune response to PCVs is associated with subsequent nasopharyngeal carriage reduction in vaccinated infants and toddlers. By combining direct and indirect protection, carriage reduction results in a reduced spread of vaccine serotypes, and eventually, a decrease in vaccine serotype disease incidence in community members of all ages. Expert opinion: The current review presents some of the aspects that influence the overall impact of PCVs on vaccine-serotype carriage, and thus, spread. The link between reduction of vaccine-serotype carriage and the eventual reduction of vaccine-serotype disease in the wider community is described by comparing data from current PCVs, specifically with respect to their ability to reduce carriage of some cross-reacting serotypes (i.e. 6A versus 6B and 19A versus 19F).
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Affiliation(s)
- Ron Dagan
- a The Faculty of Health Sciences , Ben-Gurion University of the Negev , Beer-Sheva , Israel
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9
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Vaccination can drive an increase in frequencies of antibiotic resistance among nonvaccine serotypes of Streptococcus pneumoniae. Proc Natl Acad Sci U S A 2018; 115:3102-3107. [PMID: 29511100 DOI: 10.1073/pnas.1718712115] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The bacterial pathogen Streptococcus pneumoniae is a major public health concern, being responsible for more than 1.5 million deaths annually through pneumonia, meningitis, and septicemia. Available vaccines target only a subset of serotypes, so vaccination is often accompanied by a rise in the frequency of nonvaccine serotypes. Epidemiological studies suggest that such a change in serotype frequencies is often coupled with an increase of antibiotic resistance among nonvaccine serotypes. Building on previous multilocus models for bacterial pathogen population structure, we have developed a theoretical framework incorporating variation of serotype and antibiotic resistance to examine how their associations may be affected by vaccination. Using this framework, we find that vaccination can result in a rapid increase in the frequency of preexisting resistant variants of nonvaccine serotypes due to the removal of competition from vaccine serotypes.
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Lee JK, Yun KW, Choi EH, Kim SJ, Lee SY, Lee HJ. Changes in the Serotype Distribution among Antibiotic Resistant Carriage Streptococcus pneumoniae Isolates in Children after the Introduction of the Extended-Valency Pneumococcal Conjugate Vaccine. J Korean Med Sci 2017; 32:1431-1439. [PMID: 28776337 PMCID: PMC5546961 DOI: 10.3346/jkms.2017.32.9.1431] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Accepted: 06/03/2017] [Indexed: 11/20/2022] Open
Abstract
This study investigated the serotype distribution and antimicrobial resistance of 3,820 nasopharyngeal Streptococcus pneumoniae isolates from infants and children who presented with respiratory symptoms at Seoul National University Children's Hospital from July 2010 to June 2015 after the introduction of the extended-valency pneumococcal conjugate vaccines (PCVs). Serotypes and antimicrobial susceptibility were determined using the Quellung reaction and E-test, respectively. S. pneumoniae was isolated from 397 (10.4%) specimens. The most common serotypes were 19A (14.0%), 23A (12.8%), 15B/C (10.7%), 11A (10.1%), 6C (7.8%), and 6A (6.3%) among the typeable pneumococci (n = 335). The PCV serotype proportions significantly decreased (59.1% in 2010/11 to 17.0% in 2014/15, P < 0.001), whereas the non-PCV serotype proportions significantly increased (40.9% in 2010/11 to 83.0% in 2014/15, P < 0.001). The non-susceptibility rates for penicillin (oral), penicillin (parenteral, non-meningitis), cefotaxime, and erythromycin were 97.8%, 22.8%, 27.7%, and 95.5%, respectively. The proportions of PCV serotypes responsible for non-susceptibility to penicillin (parenteral, non-meningitis) and multidrug resistance significantly decreased (80.8% to 21.1%, P < 0.001 and 64.3% to 12.3%, P < 0.001, respectively), whereas the non-PCV serotype proportions significantly increased (19.2% to 78.9%, P < 0.001 and 35.7% to 87.7%, P < 0.001, respectively). Serotypes 23A and 15B/C demonstrated significant proportional increase among the antibiotics resistant strains. Thus, the PCV serotype proportions decreased and the non-PCV serotype proportions increased among nasopharyngeal carriage pneumococci after the introduction of extended-valency PCVs in Korea. Antimicrobial non-susceptibility rates for penicillin and erythromycin remain high despite the decrease in the proportion of PCV serotypes responsible for antimicrobial resistance over time.
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Affiliation(s)
- Joon Kee Lee
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Ki Wook Yun
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Eun Hwa Choi
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Sun Jung Kim
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Seong Yeon Lee
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea
| | - Hoan Jong Lee
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
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11
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Veeraraghavan B, Jayaraman R, John J, Varghese R, Neeravi A, Verghese VP, Thomas K. Customized sequential multiplex PCR for accurate and early determination of invasive pneumococcal serotypes found in India. J Microbiol Methods 2016; 130:133-135. [DOI: 10.1016/j.mimet.2016.09.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Revised: 09/09/2016] [Accepted: 09/09/2016] [Indexed: 10/21/2022]
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12
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Hadjipanayis A, Efstathiou E, Alexandrou M, Panayiotou L, Zachariadou C, Petrou P, Papaevangelou V. Nasopharyngeal Pneumococcal Carriage among Healthy Children in Cyprus Post Widespread Simultaneous Implementation of PCV10 and PCV13 Vaccines. PLoS One 2016; 11:e0163269. [PMID: 27706247 PMCID: PMC5051711 DOI: 10.1371/journal.pone.0163269] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 09/05/2016] [Indexed: 11/19/2022] Open
Abstract
The objective of the study was to describe the incidence of pneumococcal nasopharyngeal carriage, serotype distribution and antibiotic resistance profile of pneumococcal nasopharyngeal isolates in healthy children aged 6 to 36 months following the implementation of conjugate vaccines. A nasopharyngeal swab was collected from 1105 healthy children following a stratified random sampling between September 2013 and April 2014. Demographics, vaccination status and data on possible risk factors were recorded. Isolates were serotyped and tested for antibiotic susceptibility. The nasopharyngeal carriage rate was 25.3%. Among 1105 children enrolled, 393 had received PCV13 and 685 PCV10. The prevailing isolated serotypes were: 23A (14.3%), 15A (8.9%), 6C (8.6%), 23B (7.5%), 19A (5.4%) and 15B (5%). The proportion of non-vaccine serotypes, PCV10 serotypes, PCV13 additional serotypes (3, 6A, 19A) was 76.8%, 2.1% and 10.4% respectively. Although children, who were fully or partially vaccinated with PCV13, were 63% less likely to be colonized with additional PCV13 serotypes compared to those vaccinated with PCV10, the difference is not significant (95%Cl = 0.14–1.02, p = 0.053). The highest antibiotic non-susceptible rates were found for erythromycin (28.2%) and penicillin (27.9%). The overall multidrug resistance rate was 13.2%, with serotypes 24F (4/6), 15A (14/25) and 19A (6/15) being the main contributors. Carriage rate was similar between children vaccinated with PCV10 or PCV13. The high incidence of 15A serotype which is also multidrug resistant should be underlined. Ongoing surveillance is needed to monitor the dynamics on nasopharyngeal carriage.
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Affiliation(s)
- Adamos Hadjipanayis
- Paediatric Department, Larnaca General Hospital, Larnaca, Cyprus
- European University Medical School, 6, Diogenis Street, Engomi, 1516 Nicosia, Cyprus
- * E-mail:
| | | | - Maria Alexandrou
- Microbiology Laboratory, Larnaca General Hospital, Larnaca, Cyprus
| | | | | | | | - Vasiliki Papaevangelou
- Third Department of Paediatrics, National and Kapodistrian University of Athens, General University Hospital “ATTIKON”, Athens, Greece
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Abstract
BACKGROUND Community-wide impact of pneumococcal conjugate vaccines (PCV) is conferred by reductions in vaccine-type nasopharyngeal carriage. We evaluated the impact of PCV13 on carriage of PCV13-specific types (1, 3, 5, 6A, 7F and 19A) and 6C among American Indians. METHODS A nasopharyngeal specimen was collected from community members of all ages between January 2010 and April 2012 (3 months before and 24 months after PCV13 introduction). Pneumococci were isolated by culture and serotyped using antisera. Monthly carriage prevalence and PCV13 coverage were calculated to identify the timing of vaccine impact relative to PCV13 introduction. Prevalence ratios (PRs) were used to compare PCV13-specific carriage before and in years 1 and 2 of PCV13 use. Coverage was calculated according to age and number of doses received. RESULTS 6645 participants (2859 <5 years and 3786 ≥5 years of age) provided 6628 specimens. A decline in PCV13-specific and type 6C carriage among children <5 years of age was observed 9 and 15 months after PCV13 introduction, respectively. Among underimmunized children, a decline in PCV13-specific carriage was observed 11 months after PCV13 introduction, when coverage in the community reached 58%. In year 2 of PCV13 use, PCV13-specific and 6C carriage were reduced by 60% and 70%, respectively (PCV13 specific: PR = 0.4, P < 0.001; 6C: PR = 0.3, P < 0.001) among children <5 years of age. The reduction in PCV13-specific carriage among those 5 to <8 years and 18+ years of age in year 2 of PCV13 use was not statistically significant. CONCLUSIONS PCV13 reduced PCV13-specific and 6C carriage among children <5 years of age. Low pre-PCV13 carriage prevalence of PCV13-specific types limited confirming this reduction for adults.
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Bacterial Density, Serotype Distribution and Antibiotic Resistance of Pneumococcal Strains from the Nasopharynx of Peruvian Children Before and After Pneumococcal Conjugate Vaccine 7. Pediatr Infect Dis J 2016; 35:432-9. [PMID: 26974749 PMCID: PMC4820239 DOI: 10.1097/inf.0000000000001030] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Pneumococcal conjugate vaccines (PCV) have decreased nasopharyngeal carriage of vaccine types but little data exist from rural areas. We investigated bacterial density, serotype distribution and antibiotic resistance of pneumococcal strains within the nasopharynx of young children in the Peruvian Andes, 2 years after PCV7 was introduced. METHODS Pneumococcal strains were isolated from a subset of 125 children from our Peruvian cohort, who entered the study in 2009 and had pneumococcus detected in the nasopharynx in both 2009 and during follow-up in 2011. Strains were Quellung serotyped and tested for susceptibility to antibiotics. Bacterial density was determined by quantitative polymerase chain reaction. RESULTS The prevalence of PCV7 strains decreased from 48% in 2009 to 28.8% in 2011, whereas non-PCV7 types increased from 52% to 71.2% (P = 0.002). There was a 3.5-fold increase in carriage of serotype 6C in 2011 (P = 0.026). Vaccination with PCV7 did not affect pneumococcal density in children colonized by a PCV7 type but did increase density in those colonized with a non-PCV7 type. Antibiotic resistance did not change after vaccine introduction; strains were nonsusceptible to tetracycline (97.2%), trimethoprim-sulfamethoxazole (56.4%), penicillin (34%), erythromycin (22.4%), chloramphenicol (18.8%) and clindamycin (12.4%). CONCLUSIONS Serotype replacement was observed post-PCV7 vaccination with a concomitant, not previously recognized, increased nasopharyngeal density.
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15
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Abstract
Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity. Recent studies have led to the determination of capsular polysaccharide structures for many serotypes using advanced analytical technologies, complete elucidation of genetic basis for the capsular types, and the development of highly effective pneumococcal conjugate vaccines. Conjugate vaccine use has altered the serotype distribution by either serotype replacement or switching, and this has increased the need to serotype pneumococci. Due to great advances in molecular technologies and our understanding of the pneumococcal genome, molecular approaches have become powerful tools to predict pneumococcal serotypes. In addition, more-precise and -efficient serotyping methods that directly detect polysaccharide structures are emerging. These improvements in our capabilities will greatly enhance future investigations of pneumococcal epidemiology and diseases and the biology of colonization and innate immunity to pneumococcal capsules.
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16
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Khan MN, Pichichero ME. The host immune dynamics of pneumococcal colonization: implications for novel vaccine development. Hum Vaccin Immunother 2015; 10:3688-99. [PMID: 25668673 DOI: 10.4161/21645515.2014.979631] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
The human nasopharynx (NP) microbiota is complex and diverse and Streptococcus pneumoniae (pneumococcus) is a frequent member. In the first few years of life, children experience maturation of their immune system thereby conferring homeostatic balance in which pneumococci are typically rendered as harmless colonizers in the upper respiratory environment. Pneumococcal carriage declines in many children before they acquire capsular-specific antibodies, suggesting a capsule antibody-independent mechanism of natural protection against pneumococcal carriage in early childhood. A child's immune system in the first few years of life is Th2-skewed so as to avoid inflammation-induced immunopathology. Understanding Th1/Th2 and Th17 ontogeny in early life and how adjuvant vaccine formulations shift the balance of T helper-cell differentiation, may facilitate the development of new protein-based pneumococcal vaccines. This article will discuss the immune dynamics of pneumococcal colonization in infants. The discussion aims to benefit the design and improvement of protein subunit-based next-generation pneumococcal vaccines.
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Affiliation(s)
- M Nadeem Khan
- a Center for Infectious Diseases and Immunology; Rochester General Hospital Research Institute ; Rochester , NY USA
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17
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Capsule Switching and Antimicrobial Resistance Acquired during Repeated Streptococcus pneumoniae Pneumonia Episodes. J Clin Microbiol 2015; 53:3318-24. [PMID: 26269621 DOI: 10.1128/jcm.01222-15] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2015] [Accepted: 08/03/2015] [Indexed: 01/18/2023] Open
Abstract
Streptococcus pneumoniae colonizes the nasopharyngeal mucus in healthy people and causes otitis media, pneumonia, bacteremia, and meningitis. In this study, we analyzed an S. pneumoniae strain that caused 7 repeated pneumonia episodes in an 80-month-old patient with cerebral palsy during a period of 25 months. A total of 10 S. pneumoniae strains were obtained from sputum samples, and serotype 6B was isolated from samples from the first 5 episodes, whereas serotype 6A was isolated from samples from the last 2. Whole-genome sequencing showed clonality of the 10 isolates with 10 single nucleotide polymorphisms (SNPs) in the genomes. Among these SNPs, one single point mutation in the wciP gene was presumed to relate to the serotype switching from 6B to 6A, and the other mutations in parC and gyrA were related to fluoroquinolone resistance. These results suggested that an S. pneumoniae strain, which asymptomatically colonized the patient's nasopharynx or was horizontally transmitted from an asymptomatic carrier, caused the repeated pneumonia events. Phenotypic variations in the capsule type and antimicrobial susceptibility occurred during the carrier state. Hyporesponsiveness to serotypes 6B and 6A of S. pneumoniae was found even after vaccination with the 7-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine. After an additional vaccination with the 13-valent pneumococcal conjugate vaccine, opsonic activities for both serotypes 6A and 6B significantly increased and are expected to prevent relapse by the same strain.
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18
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Roca-Oporto C, Pachón-Ibañez ME, Pachón J, Cordero E. Pneumococcal disease in adult solid organ transplantation recipients. World J Clin Infect Dis 2015; 5:1-10. [DOI: 10.5495/wjcid.v5.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 08/26/2014] [Accepted: 11/10/2014] [Indexed: 02/06/2023] Open
Abstract
In solid organ transplant (SOT) recipients, Streptococcus pneumoniae can cause substantial morbidity and mortality ranging from non-invasive to invasive diseases, including pneumonia, bacteremia, and meningitis, with a risk of invasive pneumococcal disease 12 times higher than that observed in non-immunocompromised patients. Moreover, pneumococcal infection has been related to graft dysfunction. Several factors have been involved in the risk of pneumococcal disease in SOT recipients, such as type of transplant, time since transplantation, influenza activity, and nasopharyngeal colonization. Pneumococcal vaccination is recommended for all SOT recipients with 23-valent pneumococcal polysaccharides vaccine. Although immunological rate response is appropriate, it is lower than in the rest of the population, decreases with time, and its clinical efficacy is variable. Booster strategy with 7-valent pneumococcal conjugate vaccine has not shown benefit in this population. Despite its relevance, there are few studies focused on invasive pneumococcal disease in SOT recipients. Further studies addressing clinical, microbiological, and epidemiological data of pneumococcal disease in the transplant setting as well as new strategies for improving the protection of SOT recipients are warranted.
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19
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Ahn JG, Choi SY, Kim DS, Kim KH. Changes in pneumococcal nasopharyngeal colonization among children with respiratory tract infections before and after use of the two new extended-valency pneumococcal conjugated vaccines. Infect Dis (Lond) 2015; 47:385-92. [PMID: 25712791 DOI: 10.3109/00365548.2014.1001997] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) and the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent PCV (PCV7) in May 2010 in Korea. We investigated the dynamics of pneumococcal nasopharyngeal (NP) colonization in children with a respiratory illness before and after use of PHiD-CV and PCV13. METHODS From March 2009 to December 2012 NP secretions were obtained from 2176 children aged < 5 years with respiratory diseases. We used the multiplex polymerase chain reaction (PCR) technique to determine pneumococcal serotypes. RESULTS Among the samples, 468 (21.5%) specimens were positive by multiplex PCR. The overall pneumococcal colonization rate remained stable during the 2009-2012 periods. The serotypes present in PCV7 and serotype 19A decreased in frequency from 36.8% and 26.4% in 2009 to 10.1% and 11.4% in 2012, respectively (χ(2) for trend, P < 0.001 and P = 0.007, respectively). The frequency of non-PCV13 serotypes increased from 36.8% in 2009 to 78.5% in 2012 (χ(2) for trend, P < 0.001). There was no significant difference in carriage rates of each serotype between groups of children that received PCV7, PHiD-CV, or PCV13. CONCLUSIONS Compared with the period of PCV7 vaccination, overall carriage rate was not affected by the introduction of new PCVs. However, serotype distribution now consists mostly of non-vaccine serotypes. PCVs affect mucosal immunity against Streptococcus pneumoniae (SP) in NP carriage; but, global SP colonization seems to be maintained by replacement.
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Affiliation(s)
- Jong Gyun Ahn
- From the 1 Department of Pediatrics, School of Medicine, Ewha Womans University , Seoul , Korea
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20
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Satzke C, Turner P, Virolainen-Julkunen A, Adrian PV, Antonio M, Hare KM, Henao-Restrepo AM, Leach AJ, Klugman KP, Porter BD, Sá-Leão R, Scott JA, Nohynek H, O'Brien KL. Standard method for detecting upper respiratory carriage of Streptococcus pneumoniae: updated recommendations from the World Health Organization Pneumococcal Carriage Working Group. Vaccine 2014; 32:165-79. [PMID: 24331112 DOI: 10.1016/j.vaccine.2013.08.062] [Citation(s) in RCA: 358] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Revised: 07/25/2013] [Accepted: 08/23/2013] [Indexed: 11/29/2022]
Abstract
In 2003 the World Health Organization (WHO) convened a working group and published a set of standard methods for studies measuring nasopharyngeal carriage of Streptococcus pneumoniae (the pneumococcus). The working group recently reconvened under the auspices of the WHO and updated the consensus standard methods. These methods describe the collection, transport and storage of nasopharyngeal samples, as well as provide recommendations for the identification and serotyping of pneumococci using culture and non-culture based approaches. We outline the consensus position of the working group, the evidence supporting this position, areas worthy of future research, and the epidemiological role of carriage studies. Adherence to these methods will reduce variability in the conduct of pneumococcal carriage studies undertaken in the context of pneumococcal vaccine trials, implementation studies, and epidemiology studies more generally so variability in methodology does not confound the interpretation of study findings.
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Affiliation(s)
- Catherine Satzke
- Pneumococcal Research, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC, Australia; Centre for International Child Health, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC, Australia; Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC, Australia.
| | - Paul Turner
- Microbiology Department, Angkor Hospital for Children, Siem Reap, Kingdom of Cambodia; Centre for Tropical Medicine, University of Oxford, Oxford, United Kingdom
| | - Anni Virolainen-Julkunen
- Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare, Helsinki, Finland
| | - Peter V Adrian
- MRC/Wits Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa
| | | | - Kim M Hare
- Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
| | | | - Amanda J Leach
- Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
| | - Keith P Klugman
- Rollins School of Public Health, Emory University, Atlanta, GA, USA; Respiratory and Meningeal Pathogens Research Unit, University of Witwatersrand, Johannesburg, South Africa
| | - Barbara D Porter
- Pneumococcal Research, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC, Australia
| | - Raquel Sá-Leão
- Laboratory of Molecular Microbiology of Human Pathogens, Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal
| | - J Anthony Scott
- KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya; London School of Hygiene & Tropical Medicine, London, UK
| | - Hanna Nohynek
- Vaccine Programme Unit, National Institute for Health and Welfare, Helsinki, Finland
| | - Katherine L O'Brien
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
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21
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Reisman J, Rudolph K, Bruden D, Hurlburt D, Bruce MG, Hennessy T. Risk Factors for Pneumococcal Colonization of the Nasopharynx in Alaska Native Adults and Children. J Pediatric Infect Dis Soc 2014; 3:104-11. [PMID: 26625363 PMCID: PMC6924510 DOI: 10.1093/jpids/pit069] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Accepted: 08/22/2013] [Indexed: 11/14/2022]
Abstract
BACKGROUND Alaska Native children have high invasive pneumococcal disease (IPD) rates, and lack of in-home running water has been shown to have a significant association with infection. Pneumococcal conjugate vaccines reduced IPD; however, this population saw substantial replacement disease and colonization with nonvaccine serotypes. We evaluated risk factors for nasopharyngeal pneumococcal colonization in Alaska Native adults and children. METHODS We conducted annual surveys from 2008 through 2011 of residents of all ages in 8 rural Alaskan villages. Interviews were conducted, medical charts were reviewed, and nasopharyngeal swabs were cultured for Streptococcus pneumoniae. Multivariate logistic regression models were developed for 3 age groups (under 10 years, 10-17 years, and 18 years and older) to determine risk factors for colonization. RESULTS We obtained 12 535 nasopharyngeal swabs from 4980 participants. Our population lived in severely crowded conditions, and 48% of households lacked in-home running water. In children <10 years, colonization was associated with lack of in-home running water, household crowding, and more children in the home. Pneumococcal vaccination status was not associated with colonization. In older children and adults, increased number of persons in the household was associated with pneumococcal colonization. CONCLUSIONS Higher colonization prevalence may partially explain increased IPD rates seen in those lacking in-home water services. Improving availability of sanitation services and reducing household crowding may reduce the burden of IPD in this population.
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Affiliation(s)
- Jonathan Reisman
- Department of Internal Medicine-Pediatrics, Harvard-Massachusetts General Hospital, Boston
| | - Karen Rudolph
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska
| | - Dana Bruden
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska
| | - Debby Hurlburt
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska
| | - Michael G. Bruce
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska
| | - Thomas Hennessy
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Anchorage, Alaska
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22
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Nasopharyngeal carriage of Streptococcus pneumoniae in healthy Turkish children after the addition of PCV7 to the national vaccine schedule. Eur J Pediatr 2014; 173:313-20. [PMID: 24046219 DOI: 10.1007/s00431-013-2156-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Revised: 08/22/2013] [Accepted: 08/31/2013] [Indexed: 12/28/2022]
Abstract
UNLABELLED The aim of this study was to determine serotype distribution and investigate antimicrobial resistance patterns of Streptococcus pneumoniae in healthy Turkish children in the era of community-wide pneumococcal conjugate vaccine (PCV7). The study was conducted on 1,101 healthy children less than 18 years of age. Specimens were collected with nasopharyngeal swabs between April 2011 and June 2011. Penicillin and ceftriaxone susceptibilities were determined by E-test according to the 2008 Clinical Laboratory Standards Institute, and serotypes of the isolates were determined by Quellung reaction. The nasopharyngeal pneumococcal carriage rate was 21.9 % (241/1,101). Using the meningitis criteria of minimum inhibitory concentration values, 73 % of the isolates were resistant to penicillin and 47.7 % of them were resistant to ceftriaxone. Half of all pneumococcal isolates were serotyped as 19F (15.2 %), 6A (15.2 %), 23F (10.3 %), and 6B (9.3 %) and surprisingly, no serotype 19A was isolated. Serotype coverage rates of PCV7 and non-PCV7 were 46.2 and 53.8 %, respectively. The most common penicillin- and ceftriaxone-resistant serotypes were 6A, 6B, 14, 19F, and 23F. Penicillin- and ceftriaxone-resistant isolates were more prevalent in serotypes covered by PCV7 than the non-PCV7 serotypes. CONCLUSION After the community-wide PCV7 vaccination, more non-PCV7 serotypes were isolated from the carriers compared to the time before PCV7 was used especially the serotype 6A, and the antimicrobial resistance of pneumococci was significantly increased.
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23
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Systematic review of the effect of pneumococcal conjugate vaccine dosing schedules on vaccine-type nasopharyngeal carriage. Pediatr Infect Dis J 2014; 33 Suppl 2:S152-60. [PMID: 24336057 PMCID: PMC3940522 DOI: 10.1097/inf.0000000000000083] [Citation(s) in RCA: 81] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND Pneumococcal conjugate vaccines (PCV) reduce nasopharyngeal carriage of vaccine type (VT) pneumococci, an important driver of vaccine programs' overall benefits. The dosing schedule that best reduces carriage is unclear. METHODS We performed a systematic review of English language publications from 1994 to 2010 (supplemented post hoc with studies from 2011) reporting PCV effects on VT carriage to assess variability in effect by dosing schedule. RESULTS We identified 32 relevant studies (36 citations) from 12,980 citations reviewed. Twenty-one (66%) evaluated PCV7; none used PCV10 or PCV13. Five studies evaluated 2 primary doses and 13 three primary doses. After the first year of life, 14 evaluated 3-dose primary series with PCV booster (3+1), seven 3 doses plus 23-valent polysaccharide booster "3+1PPV23," five "3+0," four "2+1," three "2+1PPV23" and two "2+0." Four studies directly compared schedules. From these, 3 primary doses reduced VT carriage more than 2 doses at 1-7 months following the series (1 study significant; 2 borderline). In a study, the 2+1 schedule reduced VT carriage more than 2+0 at 18, but not at 24 months of age. One study of a 23-valent pneumococcal polysaccharide vaccine booster showed no effect. All 16 clinical trials with unvaccinated controls and 11 observational studies with before-after designs showed reduction in VT carriage. CONCLUSIONS The available literature demonstrates VT-carriage reduction for 2+0, 2+1, 3+0 and 3+1 PCV schedules, but not for 23-valent pneumococcal polysaccharide vaccine booster. Comparisons between schedules show that 3 primary doses and a 2+1 schedule may reduce carriage more than 2 primary doses and a 2+0 schedule, respectively.
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24
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Weinberger DM, Bruden DT, Grant LR, Lipsitch M, O'Brien KL, Pelton SI, Sanders EAM, Feikin DR. Using pneumococcal carriage data to monitor postvaccination changes in invasive disease. Am J Epidemiol 2013; 178:1488-95. [PMID: 24013204 DOI: 10.1093/aje/kwt156] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Pneumococcal conjugate vaccines (PCVs) have been introduced worldwide. However, few developing countries have high-quality surveillance systems available for monitoring vaccine impact. We evaluated whether data from nasopharyngeal carriage studies can be used to accurately monitor post-PCV changes in the incidence of invasive pneumococcal disease (IPD) among children under 5 years of age. For various dates during 1991-2010, data on nasopharyngeal pneumococcal carriage and on IPD before and after administration of 7-valent PCV (PCV7) were available from England and Wales, the Netherlands, the Navajo and White Mountain Apache American Indian populations, and the US states of Massachusetts and Alaska. We estimated the change in carriage prevalence for each serotype in each study and then either calculated the average change (inverse variance-weighted) among vaccine and nonvaccine serotypes (model 1) or used mixed-effects models to estimate the change for each serotype individually, pooling serotype data within or between studies (models 2 and 3). We then multiplied these values by the proportion of IPD caused by each serotype during the pre-PCV7 period to obtain an estimate of post-PCV7 disease incidence. Model 1 accurately captured overall changes in IPD incidence following PCV7 introduction for most studies, while the more detailed models, models 2 and 3, were less accurate. Carriage data can be used in this simple model to estimate post-PCV changes in IPD incidence.
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25
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Sharma D, Baughman W, Holst A, Thomas S, Jackson D, da Gloria Carvalho M, Beall B, Satola S, Jerris R, Jain S, Farley MM, Nuorti JP. Pneumococcal carriage and invasive disease in children before introduction of the 13-valent conjugate vaccine: comparison with the era before 7-valent conjugate vaccine. Pediatr Infect Dis J 2013; 32:e45-53. [PMID: 23080290 DOI: 10.1097/inf.0b013e3182788fdd] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Nasopharyngeal (NP) carriage and invasive pneumococcal disease (IPD) attributable to serotypes in the 7-valent pneumococcal conjugate vaccine (PCV7) declined dramatically after vaccine introduction, whereas non-PCV7 serotypes increased modestly. Characteristics of pneumococcal carriage and IPD among children in Atlanta, GA, were compared during 2 time periods: before PCV7 introduction and before 13-valent PCV (PCV13) introduction. METHODS NP swabs from 231 and 451 children 6-59 months old receiving outpatient medical care were obtained in 1995 and 2009, respectively. A total of 202 and 47 IPD cases were identified in children younger than 5 years of age in 1995 and in 2008 to 2009, respectively, through active, population-based surveillance in Atlanta. Isolates were serotyped, sequence-typed (ST) and tested for antimicrobial susceptibility. RESULTS Forty percent (93/231) of children in 1995 and 31% (139/451) in 2009 were colonized with Streptococcus pneumoniae; 60% and 0.7% were PCV7 serotypes, respectively. In 1995, PCV7 serotypes accounted for 83% and 19A accounted for 5% of IPD compared with no PCV7 serotypes and 19A accounting for 49% of IPD in 2009 (P < 0.001). In 2009, PCV13 serotypes accounted for 22% of carriage (mostly 19A) and 60% of invasive isolates (P < 0.001). ST320 accounted for 66% and 52% of 19A carriage and IPD isolates in 2009, respectively; all ST320 isolates were multidrug-resistant. No ST320 NP or IPD isolates were identified before PCV7. CONCLUSIONS Serotype distribution among NP and IPD isolates in Atlanta has shifted to non-PCV7 serotypes; 19A was the leading serotype for both. The multidrug-resistant ST320 strain was responsible for two-thirds of 19A carriage isolates and half of IPD isolates. The predominance of serotype 19A in carriage and IPD among children in Atlanta highlights the potential direct and indirect benefits anticipated by implementation of PCV13 in the community.
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Affiliation(s)
- Dolly Sharma
- Emory University School of Medicine, Atlanta, GA, USA
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26
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Rudolph K, Bruce M, Bruden D, Zulz T, Wenger J, Reasonover A, Harker-Jones M, Hurlburt D, Hennessy T. Epidemiology of pneumococcal serotype 6A and 6C among invasive and carriage isolates from Alaska, 1986-2009. Diagn Microbiol Infect Dis 2012; 75:271-6. [PMID: 23276772 DOI: 10.1016/j.diagmicrobio.2012.11.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2012] [Revised: 10/19/2012] [Accepted: 11/21/2012] [Indexed: 11/19/2022]
Abstract
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.
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Affiliation(s)
- Karen Rudolph
- Arctic Investigations Program, Centers for Disease Control and Prevention, Anchorage, AK 99508, USA
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Cho EY, Kang HM, Lee J, Kang JH, Choi EH, Lee HJ. Changes in serotype distribution and antibiotic resistance of nasopharyngeal isolates of Streptococcus pneumoniae from children in Korea, after optional use of the 7-valent conjugate vaccine. J Korean Med Sci 2012; 27:716-22. [PMID: 22787364 PMCID: PMC3390717 DOI: 10.3346/jkms.2012.27.7.716] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2012] [Accepted: 03/16/2012] [Indexed: 11/20/2022] Open
Abstract
We investigated serotype distribution and antimicrobial resistance of pneumococcal carriage isolates from children after optional immunization with the 7-valent pneumococcal conjugate vaccine (PCV7) in Korea. From June 2009 to June 2010, 205 (16.5%) pneumococcal isolates were obtained from 1,243 nasopharyngeal aspirates of infants and children at Seoul National University Children's Hospital, Korea. Serotype was determined by Quellung reaction and antibiotic susceptibility was tested by E-test. The results were compared to previous studies done in the pre-PCV7 period. In this study, the most common serotypes were 6A (15.3%), 19A (14.7%), 19F (10.2%), 35B (7.3%), and 6D (5.6%). The proportion of PCV7 serotypes decreased from 61.9% to 23.8% (P < 0.001). The overall penicillin nonsusceptibility rate increased from 83.5% to 95.4% (P = 0.001). This study demonstrates the impact of optional PCV7 vaccination in Korea; the proportion of all PCV7 serotypes except 19F decreased while antimicrobial resistant serotypes 6A and 19A further increased.
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Affiliation(s)
- Eun Young Cho
- Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
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Song JH, Dagan R, Klugman KP, Fritzell B. The relationship between pneumococcal serotypes and antibiotic resistance. Vaccine 2012; 30:2728-37. [DOI: 10.1016/j.vaccine.2012.01.091] [Citation(s) in RCA: 99] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2011] [Revised: 01/31/2012] [Accepted: 01/31/2012] [Indexed: 10/28/2022]
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Abstract
BACKGROUND We sought to measure trends in Streptococcus pneumoniae carriage and antibiotic resistance in young children in Massachusetts communities after widespread adoption of heptavalent 7-valent pneumococcal conjugate vaccine (PCV7) and before the introduction of the 13-valent PCV (PCV13). METHODS We conducted a cross-sectional study including collection of questionnaire data and nasopharyngeal specimens among children aged <7 years in primary care practices from 8 Massachusetts communities during the winter season of 2008-2009 and compared with similar studies performed in 2001, 2003-2004, and 2006-2007. Antimicrobial susceptibility testing and serotyping were performed on pneumococcal isolates, and risk factors for colonization in recent seasons (2006-2007 and 2008-2009) were evaluated. RESULTS We collected nasopharyngeal specimens from 1011 children, 290 (29%) of whom were colonized with pneumococcus. Non-PCV7 serotypes accounted for 98% of pneumococcal isolates, most commonly 19A (14%), 6C (11%), and 15B/C (11%). In 2008-2009, newly targeted PCV13 serotypes accounted for 20% of carriage isolates and 41% of penicillin-nonsusceptible S. pneumoniae. In multivariate models, younger age, child care, young siblings, and upper respiratory illness remained predictors of pneumococcal carriage, despite near-complete serotype replacement. Only young age and child care were significantly associated with penicillin-nonsusceptible S. pneumoniae carriage. CONCLUSIONS Serotype replacement post-PCV7 is essentially complete and has been sustained in young children, with the relatively virulent 19A being the most common serotype. Predictors of carriage remained similar despite serotype replacement. PCV13 may reduce 19A and decrease antibiotic-resistant strains, but monitoring for new serotype replacement is warranted.
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Scott JR, Hanage WP, Lipsitch M, Millar EV, Moulton LH, Hinds J, Reid R, Santosham M, O’Brien KL. Pneumococcal sequence type replacement among American Indian children: A comparison of pre- and routine-PCV7 eras. Vaccine 2012; 30:2376-81. [DOI: 10.1016/j.vaccine.2011.11.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2011] [Revised: 11/01/2011] [Accepted: 11/01/2011] [Indexed: 11/15/2022]
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Scott JR, Millar EV, Lipsitch M, Moulton LH, Weatherholtz R, Perilla MJ, Jackson DM, Beall B, Craig MJ, Reid R, Santosham M, O'Brien KL. Impact of more than a decade of pneumococcal conjugate vaccine use on carriage and invasive potential in Native American communities. J Infect Dis 2011; 205:280-8. [PMID: 22128315 DOI: 10.1093/infdis/jir730] [Citation(s) in RCA: 85] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND We assessed the impact of 12 years of pneumococcal conjugate vaccine (PCV7) use on pneumococcal nasopharyngeal carriage and serotype-specific invasive disease potential among Native Americans. METHODS Families were enrolled in a carriage study from 2006 to 2008; nasopharyngeal specimens and risk factor information were collected monthly for 7 visits. Pneumococcal carriage prevalence was compared with that before (1998-2000) and during (2001-2002) PCV7 introduction. We compared invasive disease incidence and carriage prevalence before and after PCV7 introduction to estimate changes in serotype-specific invasive potential. RESULTS We enrolled 1077 subjects from 302 households. There was an absolute reduction in carriage prevalence of 8.0% (95% confidence interval [CI], 4.5%-11.4%) in children aged <5 years and 3.1% (95% CI, 1.1%-5.1%) in adults. In children aged <5 years, vaccine-serotype carriage prevalence decreased by 22.8% (95% CI, 20.1%-25.3%), and nonvaccine serotype (NVT) increased by 15.9% (95% CI, 12.4%-19.3%). No significant change was detected in serotype-specific invasive potential after PCV7 introduction. CONCLUSIONS Pneumococcal carriage prevalence decreased in all ages since PCV7 introduction; vaccine-serotype carriage has been nearly eliminated, whereas the prevalence of NVT carriage has increased. The increase in the NVT invasive disease rate seems to be proportional to the increase in colonization prevalence.
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Affiliation(s)
- Jennifer R Scott
- Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
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Response to “Outcomes and costs associated with PHiD-CV, a new protein D conjugate pneumococcal vaccine, in four countries”. Vaccine 2011; 29:7589-90; author reply 7591-2. [DOI: 10.1016/j.vaccine.2011.02.103] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2011] [Accepted: 02/28/2011] [Indexed: 11/23/2022]
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Greenhalgh D, Lamb KE, Robertson C. A mathematical model for the spread of Strepotococcus pneumoniae with transmission dependent on serotype. JOURNAL OF BIOLOGICAL DYNAMICS 2011; 6 Suppl 1:72-87. [PMID: 22873676 DOI: 10.1080/17513758.2011.592548] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
We examine a mathematical model for the transmission of Streptococcus Pneumoniae amongst young children when the carriage transmission coefficient depends on the serotype. Carriage means pneumococcal colonization. There are two sequence types (STs) spreading in a population each of which can be expressed as one of two serotypes. We derive the differential equation model for the carriage spread and perform an equilibrium and global stability analysis on it. A key parameter is the effective reproduction number R (e). For R (e) ≤ 1, there is only the carriage-free equilibrium (CFE) and the carriage will die out whatever be the starting values. For R (e) > 1, unless the effective reproduction numbers of the two STs are equal, in addition to the CFE there are two carriage equilibria, one for each ST. If the ST with the largest effective reproduction number is initially present, then in the long-term the carriage will tend to the corresponding equilibrium.
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Affiliation(s)
- David Greenhalgh
- Department of Mathematics and Statistics , University of Strathclyde, Livingstone Tower, 26 Richmond Street , Glasgow, UK.
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Clonal evolution leading to maintenance of antibiotic resistance rates among colonizing Pneumococci in the PCV7 era in Portugal. J Clin Microbiol 2011; 49:2810-7. [PMID: 21632898 DOI: 10.1128/jcm.00517-11] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
The introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in Portugal led to extensive serotype replacement among carriers of pneumococci, with a marked decrease of PCV7 types. Although antimicrobial resistance was traditionally associated with PCV7 types, no significant changes in the rates of nonsusceptibility to penicillin, resistance to macrolides, or multidrug resistance were observed. This study aimed to investigate the mechanisms leading to maintenance of antimicrobial resistance, despite marked serotype replacement. We compared, through molecular typing, 252 antibiotic-resistant pneumococci recovered from young carriers in 2006 and 2007 (era of high PCV7 uptake) with collections of isolates from 2002 and 2003 (n=374; low-PCV7-uptake era) and 1996 to 2001 (n=805; pre-PCV7 era). We observed that the group of clones that has accounted for antimicrobial resistance since 1996 is essentially the same as the one identified in the PCV7 era. The relative proportions of such clones have, however, evolved substantially overtime. Notably, widespread use of PCV7 led to an expansion of two Pneumococcal Molecular Epidemiology Network (PMEN) clones expressing non-PCV7 capsular variants of the original strains: Sweden(15A)ST63 (serotypes 15A and 19A) and Denmark(14)ST230 (serotypes 19A and 24F). These variants were already in circulation in the pre-PCV7 era, although they have now become increasingly abundant. Emergence of novel clones and de novo acquisition of resistance contributed little to the observed scenario. No evidence of capsular switch events occurring after PCV7 introduction was found. In the era of PCVs, antimicrobial resistance remains a problem among the carried pneumococci. Continuous surveillance is warranted to evaluate serotype and clonal shifts leading to maintenance of antimicrobial resistance.
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García-Vera C, Ruiz Andrés MÁ, Arana Navarro T, Moneo Hernández I, Castillo Laita JA, Macipe Costa R, Revillo Pinilla MJ. [Nasopharyngeal carriage of pneumococcal serotypes in healthy pre-school aged children after 7-valent pneumococcal vaccine]. Med Clin (Barc) 2011; 137:1-7. [PMID: 21514939 DOI: 10.1016/j.medcli.2010.09.051] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2010] [Revised: 09/24/2010] [Accepted: 09/28/2010] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND OBJECTIVE To determine the characteristics influencing pneumococcal serotype colonization in healthy pre-school aged children, the distribution of serotypes and their antimicrobial susceptibility, after the introduction of pneumococcal 7-valent conjugate vaccine (VNC-7 v). SUJETOS AND METHODS: Nasopharyngeal samples were collected from children under 6 years of age attending well-child examinations in the province of Zaragoza (Spain). Logistic regression was used to study different variables related to the status of the carriers. RESULTS Of the 371 children studied 30.7% were found to be carriers. With a vaccine coverage rate of 66%, factors related with presence of pneumococcal carriage were found to be the number of siblings (OR 1.44; CI 95% 1.05-1.97 for each sibling), attending a school or child day care centre (OR 3.99; CI 95% 2.00-7.96) and suffering from a minor upper respiratory tract infection (URTI) (OR 1.72; CI 95% 1.02-2.90). Only 8.7% corresponded to VNC-7 v serotypes. The most common non VNC-7 v serotypes isolated were 19A, 6A, 15B, 11, and 15A. Significantly greater resistance was detected among VNC-7 v serotypes. CONCLUSION Children in the setting of this study carried pneumococci more commonly when they have siblings, attend school or day care, or suffer from minor URTI. In the VNC-7 v vaccine era, VNC-7 v serotypes have become rare occurrences (8.7%) and emerging serotypes present better susceptibility to antibiotics.
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Beall BW, Gertz RE, Hulkower RL, Whitney CG, Moore MR, Brueggemann AB. Shifting genetic structure of invasive serotype 19A pneumococci in the United States. J Infect Dis 2011; 203:1360-8. [PMID: 21398395 DOI: 10.1093/infdis/jir052] [Citation(s) in RCA: 132] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Following 7-valent conjugate vaccine introduction in the United States in 2000, invasive serotype (sero19A) pneumococcal disease (IPD) emerged rapidly. Sero19A IPD incidence increased slightly during 2005-2008 (from 2.3 cases to 2.5 cases per 100,000 population), whereas sero19A penicillin resistance (defined as a minimum inhibitor concentration [MIC] ≥2 μg/mL) increased significantly (from 28.7% to 43.7%). To better understand changes, we characterized sero19A isolates recovered during 2004-2008. METHODS We performed antimicrobial susceptibility testing on all 2767 sero19A IPD isolates identified through the Centers for Disease Control Active Bacterial Core surveillance during 2004-2008. We genotyped 1804 (96.3%) of 1874 sero19A isolates recovered during 2005-2007 and all 148 year 2008 sero19A isolates from children <5 years of age. RESULTS Resistant clonal complex (CC) 320/271(19A) increased from 20.9% (115 of 550) to 32.9% (208 of 633; P < .001) of IPD isolates during 2005-2007, which paralleled increased sero19A penicillin resistance (from 28.7% [163 of 567 isolates] to 39.5% [261 of 661 isolates]; P < .001). Total IPD due to 320/271(19A) increased during 2005-2007 and increased from 2.1 to 3.6 cases per 100,000 population during 2005-2008 in children <5 years of age. The penicillin-susceptible/intermediate, putative vaccine-escape CC695(19A) increased from 7.5% (41 of 550) to 13.6% (85 of 633) of sero19A isolates during 2005-2007 (P = .002). CONCLUSIONS Sero19A rates may have plateaued; however, clonal shifts are increasing resistance. Increased IPD caused by CC320/271(19A) and CC695(19A) could reflect additional selective advantages in addition to resistance.
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Affiliation(s)
- Bernard W Beall
- Respiratory Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
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Abstract
Routine childhood vaccination has affected frequency and bacteriology of acute otitis media (AOM) and acute bacterial rhinosinusitis (ABRS). Routine influenza vaccination moderately reduces AOM, and the Haemophilus influenzae type b vaccine likely had a minor role in AOM and ABRS. The conjugated pneumococcal vaccine has drastically reduced invasive pneumococcal disease and caused a moderate decrease in AOM and, likely, ABRS. The vaccine serotypes of Streptococcus pneumoniae have been all but eliminated, but other serotypes have emerged as potential causes of invasive disease. Antibiotic resistance in pneumococcal disease seems to have decreased. A decrease in the overall prevalence of S. pneumoniae may have resulted in an increased incidence of Staphylococcus aureus as a pathogen in AOM and ABRS due to the concept of bacterial interference.
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Van Effelterre T, Moore MR, Fierens F, Whitney CG, White L, Pelton SI, Hausdorff WP. A dynamic model of pneumococcal infection in the United States: Implications for prevention through vaccination. Vaccine 2010; 28:3650-60. [DOI: 10.1016/j.vaccine.2010.03.030] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2009] [Revised: 03/12/2010] [Accepted: 03/15/2010] [Indexed: 10/19/2022]
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Hausdorff WP, Hoet B, Schuerman L. Do pneumococcal conjugate vaccines provide any cross-protection against serotype 19A? BMC Pediatr 2010; 10:4. [PMID: 20122261 PMCID: PMC2829470 DOI: 10.1186/1471-2431-10-4] [Citation(s) in RCA: 81] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2009] [Accepted: 02/02/2010] [Indexed: 11/10/2022] Open
Abstract
Background Introduction of the 7-valent pneumococcal conjugate vaccine (7vCRM) in several countries has led to a rapid, significant drop in vaccine-type invasive pneumococcal disease (IPD) in immunized children. In the United States and some other countries with high antibiotic use, a subsequent rise in serotype 19A IPD has been taken to indicate that the 19F conjugate in the vaccine provides no cross-protection against the immunologically related 19A. Discussion We systematically assessed the clinical efficacy and effectiveness of 19F-containing vaccines against 19A disease or nasopharyngeal carriage by searching English-language articles in the electronic databases PubMed, Current contents, Scopus, and Embase from 1985 to 2008. The vaccine efficacy and effectiveness point estimates were consistently positive for modest protection against 19A IPD and acute otitis media (AOM). However, statistical significance was not reached in any individual study. No consistent impact of 7vCRM on 19A nasopharyngeal colonization could be detected. These findings are discussed in context of immunogenicity analyses indicating that 7vCRM induces functionally active anti-19A antibodies after the booster dose, and that other 19F-containing vaccine formulations may elicit higher levels of such antibodies after both primary and booster doses. Summary Taken together, these results suggest that 19F-conjugates can provide some protection against 19A disease. The magnitude of this protection in a given setting will likely depend on several factors. These include the anti-19A immunogenicity of the specific vaccine formulation, the number of doses of that formulation needed to elicit the response, and the burden of 19A disease that occurs after those doses. It is possible that a modest protective effect may be obscured by the presence of countervailing selection pressures (such as high antibiotic use) that favor an increase in colonization with antibiotic-non-susceptible strains of 19A.
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Abstract
Septic arthritis is an infection of the joint space that requires prompt recognition by physicians. In children, the diagnosis of septic arthritis can often be challenging and delayed diagnosis can produce long-term morbidity. Posttraumatic septic arthritis is rarely reported and can be an equally challenging diagnosis. We present a case of a fully immunized 20-month-old boy with Streptococcus pneumoniae posttraumatic septic arthritis without evidence of an open fracture.
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Impact of a pneumococcal conjugate vaccination program on carriage among children in Norway. CLINICAL AND VACCINE IMMUNOLOGY : CVI 2010; 17:325-34. [PMID: 20107006 DOI: 10.1128/cvi.00435-09] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
In July 2006, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in Norway with a reduced (2 doses + 1 boost) dose schedule. Post-PCV7 shifts in pneumococcal reservoirs were assessed by two point prevalence studies of nasopharyngeal colonization among children in day care centers, before (2006) and after (2008) widespread use of PCV7. Nasopharyngeal swabs were obtained from 1,213 children, 611 in 2006 and 602 in 2008. A total of 1,102 pneumococcal isolates were recovered. Serotyping, multilocus sequence typing, and antimicrobial drug susceptibility testing were performed on all isolates. Although carriage of PCV7 serotypes decreased among both vaccinated and unvaccinated children, the overall prevalence of pneumococcal carriage remained high (80.4%) after vaccine introduction. The pneumococcal populations were diverse, and in the shift toward non-PCV7 serotypes, expansion of a limited number of established clonal complexes was observed. While non-antimicrobial-susceptible clones persisted among PCV7 serotypes, antimicrobial resistance did not increase among non-PCV7 serotypes. Direct and indirect protection of PCV7 against nasopharyngeal colonization was inferred from an overall decrease in carriage of PCV7 serotypes. No preference was found for nonsusceptible clones among the replacing non-PCV7 serotypes.
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Vestrheim DF, Høiby EA, Bergsaker MR, Rønning K, Aaberge IS, Caugant DA. Indirect effect of conjugate pneumococcal vaccination in a 2+1 dose schedule. Vaccine 2010; 28:2214-2221. [PMID: 20056192 DOI: 10.1016/j.vaccine.2009.12.054] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2009] [Revised: 11/23/2009] [Accepted: 12/23/2009] [Indexed: 02/05/2023]
Abstract
In 2006, the heptavalent pneumococcal conjugate vaccine (PCV7) was introduced in the Norwegian Childhood Vaccination Programme in a 2+1 dose schedule; immunisations are administered at 3, 5 and 12 months. Changes in invasive pneumococcal disease in all ages from the baseline years 2004-2005 to 2008 were assessed, focusing on the indirect effect in the unvaccinated population. Following the introduction of PCV7, incidence rates of IPD caused by vaccine serotypes declined across all age groups, the decline being statistically significant for the age groups <5 years, 5-19 years, 40-64 years and > or = 65 years. In the unvaccinated population aged > or = 5 years the incidence rate of IPD caused by PCV7 serotypes declined by 48% from 12.34 cases/100,000 population to 6.44 cases/100,000 population, accounting for 74% of prevented cases of IPD in 2008. Among the adults aged > or = 65 years the incidence rate of IPD caused by serotypes not included in PCV7 increased. No vaccine failure was identified, indicating a very high effectiveness of the 2+1 dose schedule vaccination programme.
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Affiliation(s)
- Didrik F Vestrheim
- Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.
| | - E Arne Høiby
- Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway
| | - Marianne R Bergsaker
- Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway
| | - Karin Rønning
- Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway
| | - Ingeborg S Aaberge
- Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway
| | - Dominique A Caugant
- Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway
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Nasopharyngeal carriage of Streptococcus pneumoniae in Gambian children who participated in a 9-valent pneumococcal conjugate vaccine trial and in their younger siblings. Pediatr Infect Dis J 2009; 28:990-5. [PMID: 19536041 DOI: 10.1097/inf.0b013e3181a78185] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Nasopharyngeal carriage of Streptococcus pneumoniae is extremely prevalent in The Gambia. We studied the effects of vaccination with pneumococcal conjugate vaccines on the carriage of individual serotypes and on antimicrobial resistance in vaccinated children and their younger siblings. METHODS A longitudinal study of a subsample of children (n=2342) who participated in a randomized, placebo controlled trial of a 9-valent pneumococcal conjugate vaccines (PCV-9) in The Gambia, and a cross-sectional study of non-PCV-9-vaccinated younger siblings (n=675). RESULTS Recipients of PCV-9 were less likely to carry vaccine serotypes 4, 6B, 9V, 14, 19F, and 23F but more likely to carry vaccine-associated 19A and 9 nonvaccine serotypes at approximately 6 months postvaccination (age, 12 months) than were controls (each P<0.05). At approximately 16 months postvaccination, carriage of vaccine-associated-serotype 6A was also significantly reduced (P<0.01) while 3 other nonvaccine serotypes were more prevalent in the PCV-9 recipients (each P<0.05). At 16 months, but not 6 months, postvaccination PCV-9 recipients had lower rate of carrying isolates resistant to tetracycline and trimethoprim-sulfamethoxazole (TMP-SMZ) than controls (risk ratio: 0.90 and 0.95, respectively; each P<0.05). There was no difference in patterns of carriage of pneumococci in younger siblings of PCV-9 or placebo recipients. CONCLUSIONS The effects of 9-valent pneumococcal conjugate vaccines on carriage of pneumococci persisted for at least 16 months postvaccination in Gambian children. Vaccination had no indirect effect on carriage in younger siblings and there was limited impact on antibiotic resistance.
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Emergence of invasive pneumococcal disease caused by multidrug-resistant serotype 19A among children in Barcelona. J Infect 2009; 59:75-82. [DOI: 10.1016/j.jinf.2009.05.012] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2008] [Revised: 04/30/2009] [Accepted: 05/31/2009] [Indexed: 11/24/2022]
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Huang SS, Hinrichsen VL, Stevenson AE, Rifas-Shiman SL, Kleinman K, Pelton SI, Lipsitch M, Hanage WP, Lee GM, Finkelstein JA. Continued impact of pneumococcal conjugate vaccine on carriage in young children. Pediatrics 2009; 124:e1-11. [PMID: 19564254 PMCID: PMC2782668 DOI: 10.1542/peds.2008-3099] [Citation(s) in RCA: 222] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVES The goals were to assess serial changes in Streptococcus pneumoniae serotypes and antibiotic resistance in young children and to evaluate whether risk factors for carriage have been altered by heptavalent pneumococcal conjugate vaccine (PCV7). METHODS Nasopharyngeal specimens and questionnaire/medical record data were obtained from children 3 months to <7 years of age in primary care practices in 16 Massachusetts communities during the winter seasons of 2000-2001 and 2003-2004 and in 8 communities in 2006-2007. Antimicrobial susceptibility testing and serotyping were performed with S pneumoniae isolates. RESULTS We collected 678, 988, and 972 specimens during the sampling periods in 2000-2001, 2003-2004, and 2006-2007, respectively. Carriage of non-PCV7 serotypes increased from 15% to 19% and 29% (P < .001), with vaccine serotypes decreasing to 3% of carried serotypes in 2006-2007. The relative contribution of several non-PCV7 serotypes, including 19A, 35B, and 23A, increased across sampling periods. By 2007, commonly carried serotypes included 19A (16%), 6A (12%), 15B/C (11%), 35B (9%), and 11A (8%), and high-prevalence serotypes seemed to have greater proportions of penicillin nonsusceptibility. In multivariate models, common predictors of pneumococcal carriage, such as child care attendance, upper respiratory tract infection, and the presence of young siblings, persisted. CONCLUSIONS The virtual disappearance of vaccine serotypes in S pneumoniae carriage has occurred in young children, with rapid replacement with penicillin-nonsusceptible nonvaccine serotypes, particularly 19A and 35B. Except for the age group at highest risk, previous predictors of carriage, such as child care attendance and the presence of young siblings, have not been changed by the vaccine.
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Affiliation(s)
- Susan S. Huang
- Division of Infectious Diseases, University of California, Irvine School of Medicine, Irvine, California,Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Virginia L. Hinrichsen
- Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, Massachusetts
| | - Abbie E. Stevenson
- Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts
| | - Sheryl L. Rifas-Shiman
- Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, Massachusetts
| | - Ken Kleinman
- Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, Massachusetts
| | - Stephen I. Pelton
- Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts
| | - Marc Lipsitch
- Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts,Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
| | - William P. Hanage
- Department of Infectious Disease Epidemiology, Imperial College, London, England
| | - Grace M. Lee
- Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, Massachusetts
| | - Jonathan A. Finkelstein
- Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, Massachusetts,Department of Pediatrics, Harvard Medical School, Boston, Massachusetts,Division of General Pediatrics, Children's Hospital Boston, Boston, Massachusetts
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Bratcher PE, Park IH, Hollingshead SK, Nahm MH. Production of a unique pneumococcal capsule serotype belonging to serogroup 6. MICROBIOLOGY-SGM 2009; 155:576-583. [PMID: 19202106 DOI: 10.1099/mic.0.024521-0] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Serogroup 6 of Streptococcus pneumoniae contains three serotypes, named 6A, 6B and 6C, with highly homologous capsule gene loci. The 6A and 6B capsule gene loci consistently differ from each other by only one nucleotide in the wciP gene. The 6A capsule gene locus has a galactosyltransferase, which has been replaced with a glucosyltransferase in the 6C capsule gene locus. We considered that a new serotype named '6X1' would be possible if the galactosyltransferase of the 6B capsule gene locus is replaced with the glucosyltransferase of 6C. We demonstrate that this gene transfer yields a viable pneumococcal strain and that the capsular polysaccharide (PS) from this strain has the predicted chemical structure and serological similarity to the capsular PS of the 6B serotype. The new strain (i.e. serotype 6X1) is typed as 6B by the quellung reaction, but it can be distinguished from 6B strains with mAbs to 6B PS. Reexamination of 264 pneumococcal isolates that had been previously typed as 6B with classical typing methods revealed no isolates expressing serotype 6X1. Nevertheless, this study shows that this capsular PS is biochemically possible and could exist/emerge in nature.
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Affiliation(s)
- Preston E Bratcher
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - In H Park
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Susan K Hollingshead
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Moon H Nahm
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.,Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Nahm MH, Lin J, Finkelstein JA, Pelton SI. Increase in the prevalence of the newly discovered pneumococcal serotype 6C in the nasopharynx after introduction of pneumococcal conjugate vaccine. J Infect Dis 2009; 199:320-5. [PMID: 19099489 DOI: 10.1086/596064] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
BACKGROUND Because pneumococcal serotype 6C was previously not distinguished from serotype 6A, the impact of the 7-valent pneumococcal conjugate vaccine (PCV7) on the carriage of serotype 6C is unknown. METHODS The nasopharyngeal (NP) prevalence of the 6C serotype was determined using 1326 pneumococcal isolates collected from 7 cohorts of Massachusetts children between 1994 and 2007. Initially, the isolates were serotyped using the quellung reaction; subsequently, stored specimens of all putative 6A isolates were tested for 6C using monoclonal antibodies. The opsonophagocytic and antibiotic susceptibilities of the isolates were determined. RESULTS The prevalence of 6A was 9.6% (33/343) before 2001, 8.0% (18/226) in 2004, and 2.9% (12/416) in 2007. In contrast, the prevalence of 6C was 0.6% (2/343) before 2001, 2.2% (5/226) in 2004, and 8.7% (36/416) in 2007 (P<.001 for 2/343 vs. 36/416). 6C isolates from 2007 were more susceptible to antibiotics than were 6A isolates. PCV7 induced a low ability to opsonize different isolates of 6C. CONCLUSIONS Among NP isolates, the prevalence of 6C isolates has increased and the prevalence of 6A isolates has decreased since the introduction of PCV7 in Massachusetts in 2000. The observed increase in serotype 6C prevalence may be explained by the induction by PCV7 of low amounts of functional anti-6C antibody, compared with anti-6A and anti-6B antibodies.
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Affiliation(s)
- Moon H Nahm
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
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Impact of conjugate pneumococcal vaccines on antibiotic resistance. THE LANCET. INFECTIOUS DISEASES 2008; 8:785-95. [DOI: 10.1016/s1473-3099(08)70281-0] [Citation(s) in RCA: 181] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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