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Matza LS, Howell TA, Chun B, Hetherington L, White M, Weiss T, Huang M, Rowen D, Tan T, Feemster K, Nozad B, Kelly MS, Hoberman A, Mohanty S. Health state utilities associated with invasive pneumococcal disease, pneumonia, and recurrent acute otitis media in young children. Qual Life Res 2025; 34:809-821. [PMID: 39751917 PMCID: PMC11920316 DOI: 10.1007/s11136-024-03840-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/07/2024] [Indexed: 01/04/2025]
Abstract
PURPOSE Cost-utility analyses examining the value of new vaccines for pneumococcal disease will require health state utilities as inputs. Existing utilities for pneumococcal infections in young children are limited. The purpose of this study was to estimate health state utilities associated with pneumococcal infections in young children. METHODS Six health state vignettes depicting infections due to Streptococcus pneumoniae were drafted based on published literature and clinician interviews. To address methodological challenges in estimating utilities for temporary infections in children 0-5 years of age, several time trade-off approaches were explored in a pilot study (N = 28 participants). In the subsequent utility elicitation study conducted in the UK, health states were valued using the best performing method from the pilot (10-year time horizon, with infections repeated annually) with adult general population respondents imagining a child 2-5 years of age. RESULTS A total of 208 participants completed interviews (51.9% female; mean [SD] age = 41.0 [14.9] years). Mean (SD) utilities were 0.902 (0.092) for pneumonia requiring hospitalization, 0.901 (0.087) for bacteremia, 0.894 (0.103) for recurrent acute otitis media (AOM), 0.882 (0.107) for recurrent AOM treated with pressure equalization tubes, 0.878 (0.109) for bacteremic pneumonia, and 0.809 (0.145) for meningitis. CONCLUSION Lower health state utilities were associated with health states that had longer treatment periods, required more invasive treatment, and described more severe infections. Utilities from this study can be used in models examining cost-effectiveness of pneumococcal vaccines. These results have methodological implications for future research estimating utilities associated with temporary pediatric health conditions.
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Affiliation(s)
- Louis S Matza
- Patient-Centered Research, Evidera, 929 N Front St., Wilmington, NC, 28401, USA.
| | - Timothy A Howell
- Patient-Centered Research, Evidera, 929 N Front St., Wilmington, NC, 28401, USA
| | | | | | | | | | - Min Huang
- MRL, Merck & Co., Inc., Rahway, NJ, USA
| | - Donna Rowen
- Sheffield Centre for Health and Related Research, University of Sheffield, Sheffield, UK
| | - Tina Tan
- Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | | | | | - Matthew S Kelly
- Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA
| | - Alejandro Hoberman
- Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
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Massora S, Mucavele H, Carvalho MDG, Mandomando I, Chaúque A, Moiane B, Tembe N, Omer SB, Bassat Q, Verani JR, Menéndez C, Quintó L, Sigaúque B, Bardají A. Effect of the Ten-valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease and Pneumonia in Infants Younger Than Ten Weeks of Age in Southern Mozambique: A Population-based Prospective Surveillance Study. Pediatr Infect Dis J 2025; 44:S75-S79. [PMID: 39951078 PMCID: PMC11966382 DOI: 10.1097/inf.0000000000004638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/12/2025]
Abstract
BACKGROUND Mozambique introduced 10-valent-pneumococcal conjugate vaccine (PCV10) in 2013. We aimed to evaluate the indirect effect of PCV10 on invasive pneumococcal disease (IPD) and clinical severe pneumonia (CSP) in infants aged less than 10 weeks. METHODS Routine surveillance data for IPD and CSP among admitted infants less than 10 weeks of age were analyzed to compare IPD and CSP incidence using demographic surveillance data from pre- and post-PCV10 periods. IPD was defined as isolation of pneumococcus from blood or cerebrospinal fluid, and CSP according to World Health Organization criteria. RESULTS The incidence of IPD and CSP among infants less than 10 weeks decreased by 87% [incidence rate ratio (IRR): 0.13; 95% confidence interval (CI): 0.02-0.95] from 283/100,000 in the pre-PCV to 36/100,000 children year at risk (CYAR) post-PCV, and by 62% (IRR: 0.38; 95% CI: 0.27-0.52) from 4100/100,000 pre-PCV to 1550/100,000 CYAR post-PCV periods, respectively. Vaccine-type IPD incidence declined by 92% (IRR: 0.18; 95% CI: 0.02-1.34) from 205/100,000 pre-PCV to 36/100,000 CYAR post-PCV, though the reduction was not statistically significant. The mortality rate due to IPD among infants less than 10 weeks declined from 47/100,000 CYAR in the pre-PCV to 0 in the post-PCV period. Mortality due to CSP declined by 29% (IRR: 0.71; 95% CI: 0.34-1.50), from 457/100,000 CYAR in the pre-PCV to 324/100,000 in the post-PCV periods. CONCLUSIONS PCV10 introduction led to substantial declines in the incidence of IPD, CSP and associated mortality in infants too young to be vaccinated (less than 10 weeks) in Mozambique, suggesting indirect protection.
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Affiliation(s)
- Sérgio Massora
- Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Moçambique
| | - Hélio Mucavele
- Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Moçambique
| | - Maria da Gloria Carvalho
- Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Division of Bacterial Diseases, Respiratory Diseases Branch, Atlanta, Georgia
| | - Inácio Mandomando
- Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Moçambique
| | - Alberto Chaúque
- Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Moçambique
| | - Benild Moiane
- Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Moçambique
| | - Nelson Tembe
- Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Moçambique
- Instituto Nacional de Saúde, Ministério de Saúde, Maputo, Mozambique
| | - Saad B. Omer
- Peter O’Donnell Jr School of Public Health, Dallas, Texas
| | - Quique Bassat
- Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Moçambique
- ISGlobal, Hospital Clínic – Universitat de Barcelona, Barcelona, Spain
- ICREA, Barcelona, Spain
- Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain
- Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Jennifer R. Verani
- Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Division of Bacterial Diseases, Respiratory Diseases Branch, Atlanta, Georgia
| | - Clara Menéndez
- Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Moçambique
- ISGlobal, Hospital Clínic – Universitat de Barcelona, Barcelona, Spain
- Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Llorenç Quintó
- Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Moçambique
- ISGlobal, Hospital Clínic – Universitat de Barcelona, Barcelona, Spain
- Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Betuel Sigaúque
- Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Moçambique
- John Snow Inc. (JSI) on the Maternal and Child Survival Program–MCSP (USAID Grantee), Maputo, Mozambique
| | - Azucena Bardají
- Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Moçambique
- ISGlobal, Hospital Clínic – Universitat de Barcelona, Barcelona, Spain
- Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
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Hsiao A, Lewis N, Hansen J, Timbol J, Suaya JA, Alexander-Parrish R, Grant LR, Gessner BD, Klein NP. Effectiveness of 13-valent pneumococcal conjugate vaccine against vaccine-type invasive pneumococcal disease in older adults. Vaccine 2025; 44:126543. [PMID: 39637487 DOI: 10.1016/j.vaccine.2024.126543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 11/14/2024] [Accepted: 11/17/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND In 2014, the Advisory Committee on Immunization Practices recommended routine use of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults age ≥ 65 years. Incidence of most PCV13-serotype cases declined, however serotype 3 cases have persisted. We estimated PCV13 vaccine effectiveness (VE) against PCV13-serotypes and serotype 3 invasive pneumococcal disease (IPD) among Kaiser Permanente Northern California (KPNC) adults. METHODS This observational study included adults ≥65 years between September 1, 2014-December 31, 2020. We used active laboratory-based surveillance to identify and serotype all Streptococcus pneumoniae isolates obtained from normally-sterile sites. We estimated the odds ratio (OR) of vaccine-type IPD using conditional logistic regression stratified by age and calendar day, adjusting for sex, age, race, ethnicity, influenza vaccine receipt, 23-valent pneumococcal polysaccharide vaccine receipt since age 65, pneumonia risk factors, healthcare utilization, and KPNC service area. We estimated VEAdjusted as (1-ORAdjusted) × 100 %. RESULTS There were 610,576 adults ≥65 years in the study population. By the end of the study period, PCV13 coverage was nearly 80 %. There were 307 IPD cases during the study period, of which 98 (31.9 %) were serotype 3. PCV13 was associated with a VEAdjusted of 61.5 % (95 % CI: 36.2, 76.7; p < 0.001) against PCV13-serotype IPD and 46.3 % (95 % CI: -2.4, 77.9; p = 0.06) against serotype 3 IPD. CONCLUSIONS PCV13 vaccination protected adults ≥65 years against IPD due to PCV13 serotypes. Continued surveillance will be critical in the ≥65-year-old population to assess the impact of higher valent PCVs on IPD serotype distribution, including individual serotypes such as serotype 3.
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Affiliation(s)
- Amber Hsiao
- Kaiser Permanente Vaccine Study Center, Oakland, CA, USA.
| | - Ned Lewis
- Kaiser Permanente Vaccine Study Center, Oakland, CA, USA
| | - John Hansen
- Kaiser Permanente Vaccine Study Center, Oakland, CA, USA
| | - Julius Timbol
- Kaiser Permanente Vaccine Study Center, Oakland, CA, USA
| | - Jose A Suaya
- Heller School, Brandeis University, Waltham, MA, USA
| | | | - Lindsay R Grant
- Pfizer Vaccine Medicines Development & Scientific Clinical Affairs, Collegeville, PA, USA
| | - Bradford D Gessner
- Pfizer Vaccine Medicines Development & Scientific Clinical Affairs, Collegeville, PA, USA
| | - Nicola P Klein
- Kaiser Permanente Vaccine Study Center, Oakland, CA, USA
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Morimoto K, Masuda S. Pneumococcal vaccines for prevention of adult pneumonia. Respir Investig 2025; 63:96-101. [PMID: 39672073 DOI: 10.1016/j.resinv.2024.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 11/27/2024] [Accepted: 12/05/2024] [Indexed: 12/15/2024]
Abstract
Streptococcus pneumoniae, pneumococcus, is one of most important bacterial pathogens in adult community-acquired pneumonia. Although it can cause a variety of illness including invasive diseases (IPD), pneumonia has a greater impact than IPD from the perspective of health economics. 23 valent pneumococcal polysaccharide vaccine (PPSV23) and 13 valent pneumococcal conjugate vaccine (PCV13) have been recommended for people ≥65 years old until recently based on evidence in preventing IPD and pneumonia. Because the introduction and dissemination of PCVs for infants and its effects on herd immunity have led 'serotype replacement' in adult IPD and pneumococcal pneumonia since the 2000s, serotypes targeted by vaccines have sifted accordingly. With the availability of PCV21 this year, in addition to PCV15 and PCV20, vaccine prevention strategies for adult pneumococcal pneumonia need to be reconsidered. In this narrative review, we discuss current and future challenges regarding pneumococcal vaccines to prevent adult pneumococcal pneumonia.
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Affiliation(s)
- Konosuke Morimoto
- Department of Respiratory Infections, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki-city, Nagasaki, 852-8523, Japan.
| | - Shingo Masuda
- Department of Respiratory Infections, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki-city, Nagasaki, 852-8523, Japan; Department of Clinical Tropical Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki-city, Nagasaki, 852-8523, Japan
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Beissegulova G, Ramazanova B, Mustafina K, Begadilova T, Koloskova Y, Seitkhanova B, Mamatova A, Iskakova U, Sailaubekuly R, Seiitbay Z. Prevalence of nasopharyngeal Streptococcus Pneumoniae carriage in infants: A systematic review and meta-analysis of cohort studies and randomized controlled trials. PLoS One 2024; 19:e0315461. [PMID: 39693316 PMCID: PMC11654947 DOI: 10.1371/journal.pone.0315461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 11/26/2024] [Indexed: 12/20/2024] Open
Abstract
This study aims to examine the prevalence of nasopharyngeal Streptococcus pneumoniae carriage (NSPC) in infants during their first two years of life and to compare the carriage rates among different vaccine groups and country income-levels. This will be achieved through a systematic review of the published literature, specifically focusing on data from cohort studies and randomized controlled trials. A comprehensive search was conducted in four electronic databases: PubMed, Web of Science, ScienceDirect, and Scopus, using a predefined search strategy. Forty-nine articles met the inclusion criteria for this systematic review. According to the results obtained from the random effects model, the pooled mean prevalence of NSPC was 1.68% at birth (95% CI [0.50; 5.47]), 24.38% at 1 to 4 months (95% CI [19.06; 30.62]), 48.38% at 4 to 6 months (95% CI [41.68; 55.13]), 59.14% at 7 to 9 months (95% CI [50.88; 66.91]), 48.41% at 10 to 12 months (95% CI [41.54; 55.35]), 42.00% at 13 to 18 months (95% CI [37.01; 47.16]), and 48.34% at 19 to 24 months (95% CI [38.50; 58.31]). The highest NSPC rates were observed among children aged 4 to 6 months and 7 to 9 months across all vaccine groups. Low-income countries consistently demonstrated the highest NSPC rates across all age categories studied. This systematic review and meta-analysis provide robust evidence of the high prevalence of NSPC in infants aged 4 to 6 months and 7 to 9 months in all vaccine groups, with persistent regional disparities, especially among low-income countries. The study highlights the need for continuous monitoring of NSPC trends, particularly the emergence of non-vaccine serotypes. Policymakers and healthcare providers should leverage these findings to enhance vaccination strategies, aiming to minimize the overall burden of pneumococcal diseases in infants.
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Affiliation(s)
- Gulzhan Beissegulova
- Department of Microbiology and Virology, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
| | - Bakyt Ramazanova
- Department of Microbiology and Virology, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
| | - Kamilya Mustafina
- Department of Microbiology and Virology, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
| | - Tolkyn Begadilova
- Department of Microbiology and Virology, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
| | - Yekaterina Koloskova
- Department of Microbiology and Virology, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
| | - Bibigul Seitkhanova
- Department of Microbiology, Virology and Immunology, South Kazakhstan Medical Academy, Shymkent, Kazakhstan
| | - Aliya Mamatova
- Department of Microbiology and Virology, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
| | - Ulzhan Iskakova
- Department of Microbiology and Virology, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
| | - Ratbek Sailaubekuly
- Department of Microbiology, Virology and Immunology, South Kazakhstan Medical Academy, Shymkent, Kazakhstan
| | - Zhaksylyk Seiitbay
- School of General Medicine-2, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
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Umana E, Mills C, Norman-Bruce H, Mitchell H, McFetridge L, Lynn F, McKeeman G, Foster S, Barrett MJ, Roland D, Lyttle MD, Watson C, Waterfield T. Performance of clinical decision aids (CDA) for the care of young febrile infants: a multicentre prospective cohort study conducted in the UK and Ireland. EClinicalMedicine 2024; 78:102961. [PMID: 39677360 PMCID: PMC11638619 DOI: 10.1016/j.eclinm.2024.102961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 11/05/2024] [Accepted: 11/08/2024] [Indexed: 12/17/2024] Open
Abstract
Background Between 1% and 4% of febrile infants, aged from birth to 90 days of age, presenting to hospital will be diagnosed with an invasive bacterial infection (IBI). Traditional teaching has advocated a treat all approach but more recently a number of clinical decision aids (CDA) have been developed to classify febrile infants into lower and higher risk cohorts, with lower risk infants suitable for management without immediate parenteral antibiotics and lumbar puncture. The aim of this study was to apply these CDA to a UK and Irish cohort. Methods This was a prospective multicentre cohort study of febrile infants presenting to 35 Paediatric Emergency Research in the UK and Ireland (PERUKI) sites between the 6th July 2022 and the 31st August 2023. All infants received standard care as per local policy. IBI was defined as growth of bacterial pathogen in blood or cerebrospinal fluid. The performance of the following CDAs were assessed, National Institute for Health and Care Excellence (NICE) guidelines NG143 (Fever under 5 years), British Society Antimicrobial Chemotherapy (BSAC), Aronson rule and American Academy of Pediatrics (AAP) CDA. A cost comparison of each CDA against a treat all approach was conducted. Trial registration: NCT05259683. Findings 1821 were included in the final analysis. The median age was 46 days (IQR: 30-64 days), with 1108 (61%) being male. Of the 1821 infants, 67 (3.7%) had IBI. The AAP and BSAC CDAs were the most sensitive at 0.99 (95% CI 0.92-1.0) for both with specificities of 0.23 (95% CI 0.21-0.25) and 0.20 (95% CI 0.18-0.22) respectively. The NICE NG143 and Aronson CDA were the most specific CDAs with values of 0.27 (95% CI 0.25-0.30) and 0.30 (95% CI 0.28-0.32) respectively, but their sensitivity was lower. The AAP CDA performed equally well with either procalcitonin (PCT) or C-reactive protein (CRP) as the biomarker of choice. Of the 1821 infants, 77% were admitted, 14% were discharged and 9% were ambulated. All CDAs were cost saving for hospital services when compared to a treat all approach, with the lowest mean cost per patient estimated for Aronson (£1171; bootstrap 95% CI £1129-£1214) and NICE NG143 CDA (£1218; bootstrap 95% CI £1174-£1263). Interpretation The AAP and BSAC CDAs are highly sensitive at excluding IBI, with a cost saving to hospital services when compared to a treat all approach. The substitution of CRP for PCT made no difference to the performance of the AAP CDA in this cohort and was more costly. Funding The Febrile Infant Diagnostic Assessment and Outcome (FIDO) study is funded by Royal College of Emergency Medicine Doctoral Fellowship (RCEM 02/03/2021). Procalcitonin analysis was supported by the Public Health Agency Northen Ireland Grant (HSC R&D-COM/5745/22). The funders played no part in the conception or design of this study.
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Affiliation(s)
- Etimbuk Umana
- Wellcome Wolfson Institute of Experimental Medicine, Queen's University Belfast, Belfast, UK
| | - Clare Mills
- Wellcome Wolfson Institute of Experimental Medicine, Queen's University Belfast, Belfast, UK
| | - Hannah Norman-Bruce
- Wellcome Wolfson Institute of Experimental Medicine, Queen's University Belfast, Belfast, UK
| | - Hannah Mitchell
- Mathematical Sciences Research Centre, Queen's University Belfast, Belfast, UK
| | - Lisa McFetridge
- Mathematical Sciences Research Centre, Queen's University Belfast, Belfast, UK
| | - Fiona Lynn
- School of Nursing and Midwifery, Queen's University Belfast, Belfast, UK
| | - Gareth McKeeman
- Department of Clinical Biochemistry, Belfast Health and Social Care Trust, Belfast, UK
| | - Steven Foster
- Emergency Department, Royal Hospital for Children, Glasgow, UK
| | - Michael J Barrett
- Paediatric Emergency Medicine, Children's Health Ireland at Crumlin, Dublin, Ireland
- Women's and Children's Health, School of Medicine, University College Dublin, Ireland
| | - Damian Roland
- Sapphire Group, Health Sciences, University of Leicester, Leicester, UK
- Paediatric Emergency Medicine Leicester Academic (PEMLA) Group, University Hospitals of Leicester NHS Trust Leicester, UK
| | - Mark D Lyttle
- Emergency Department, Bristol Royal Hospital for Children, Bristol, UK
- Faculty of Health and Applied Sciences, University of the West of England, Bristol, UK
| | - Chris Watson
- Wellcome Wolfson Institute of Experimental Medicine, Queen's University Belfast, Belfast, UK
| | - Thomas Waterfield
- Wellcome Wolfson Institute of Experimental Medicine, Queen's University Belfast, Belfast, UK
- Emergency Department, Royal Belfast Hospital for Sick Children, Belfast, UK
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Hausdorff WP, Madhi SA, Kang G, Kaboré L, Tufet Bayona M, Giersing BK. Facilitating the development of urgently required combination vaccines. Lancet Glob Health 2024; 12:e1059-e1067. [PMID: 38636529 PMCID: PMC11099297 DOI: 10.1016/s2214-109x(24)00092-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 01/25/2024] [Accepted: 02/22/2024] [Indexed: 04/20/2024]
Abstract
The essence of a vaccine lies in its ability to elicit a set of immune responses specifically directed at a particular pathogen. Accordingly, vaccines were historically designed, developed, registered, recommended, procured, and administered as monopathogen formulations. Nonetheless, the control and elimination of an astonishing number of diseases was realised only after several once-separate vaccines were provided as combinations. Unfortunately, the current superabundance of recommended and pipeline vaccines is now at odds with the number of acceptable vaccine administrations and feasible health-care visits for vaccine recipients and health-care providers. Yet, few new combinations are in development because, in addition to the scientific and manufacturing hurdles intrinsic to coformulation, developers face a gauntlet of regulatory, policy, and commercialisation obstacles in a milieu still largely designed for monopathogen vaccines. We argue here that national policy makers and public health agencies should prospectively identify and advocate for the development of new multipathogen combination vaccines, and suggest ways to accelerate the regulatory pathways to licensure of combinations and other concrete, innovative steps to mitigate current obstacles.
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Affiliation(s)
- William P Hausdorff
- Center for Vaccine Innovation and Access, PATH, Washington, DC, USA; Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
| | - Shabir A Madhi
- South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Johannesburg, South Africa
| | | | - Lassané Kaboré
- PATH, Center for Vaccine Innovation and Access, Dakar, Senegal; Gavi, The Vaccine Alliance, Geneva, Switzerland
| | | | - Birgitte K Giersing
- WHO Department of Immunization, Vaccines and Biologicals, Geneva, Switzerland
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8
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Rachad S, Nickel D, Berry F, Goddard M, Khan A, Muratori N, Hymes S, Ata A, Woll C. Risk of serious bacterial infections in pediatric patients with hyperpyrexia. J Am Coll Emerg Physicians Open 2024; 5:e13135. [PMID: 38481522 PMCID: PMC10936538 DOI: 10.1002/emp2.13135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 02/19/2024] [Indexed: 11/02/2024] Open
Abstract
Objectives Hyperpyrexia has been associated with a greater prevalence of bacterial infections in the pediatric population, which prior to routine childhood vaccinations, has led to invasive testing and empiric antibiotic use for urinary tract infections, bacterial pneumonia, bacteremia, and bacterial meningitis. Since the implementation of routine childhood vaccinations, the prevalence of serious bacterial infections (SBIs) has declined. This study aims to determine if there is an association between hyperpyrexia and serious bacterial infections in well-appearing febrile pediatric patients presenting to the emergency department (ED). Methods This is a cross-sectional study conducted between January 1, 2019, and December 31, 2019, at a single urban tertiary care pediatric ED. Patients were included if they were between 61 days and ≤18 years old presenting with a chief complaint of fever. Patients were excluded if they received antibiotics within 3 days of presentation, underwent surgical procedures within 2 weeks of presentation, had an ED visit for febrile illness within 2 weeks of study visit, were transferred from another institution, or were ill appearing. Prevalence of SBI was described and compared by presence of hyperpyrexia, age group, chronic medical condition, gender, and vaccination status. Logistic regression was used to analyze the association between SBIs and hyperpyrexia. Results Of the 3862 charts reviewed, 2565 patients were included. The prevalence of SBI was 5.6%. A total of 413 patients presented with hyperpyrexia. Of the patients with hyperpyrexia, 31 (7.5%) had a serious bacterial infection. Hyperpyrexia was not significantly associated with SBIs in our logistic regression models (adjusted Odds Ratio 1.40, 95% confidence interval 0.92-2.12). Conclusions Serious bacterial infections were uncommon in our population. There is no statistically significant association between hyperpyrexia and SBIs in well-appearing pediatric patients presenting to the ED with fever. The lack of a statistically significant association between hyperpyrexia and SBIs argues that clinicians should be cautious using hyperpyrexia as an independent risk factor for SBIs. More research is needed to identify independent and grouped SBI risk factors in well-appearing pediatric patients presenting to the ED.
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Affiliation(s)
| | - Dane Nickel
- Department of Emergency MedicineState University of New York Upstate Medical UniversitySyracuseNew YorkUSA
| | | | | | - Ayesha Khan
- Department of Emergency MedicineStanford MedicinePalo AltoCaliforniaUSA
| | | | - Saul Hymes
- Department of PediatricsAlbany Medical CenterAlbanyNew YorkUSA
| | - Ashar Ata
- Department of Surgery and Emergency MedicineAlbany Medical CenterAlbanyNew YorkUSA
| | - Christopher Woll
- Department of PediatricsAlbany Medical CenterAlbanyNew YorkUSA
- Department of Emergency MedicineAlbany Medical CenterAlbanyNew YorkUSA
- Double H RanchLake LuzerneNew YorkUSA
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9
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Feemster K, Weaver J, Buchwald U, Banniettis N, Cox KS, McIntosh ED, Spoulou V. Pneumococcal Vaccine Breakthrough and Failure in Infants and Children: A Narrative Review. Vaccines (Basel) 2023; 11:1750. [PMID: 38140155 PMCID: PMC10747311 DOI: 10.3390/vaccines11121750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 11/20/2023] [Accepted: 11/21/2023] [Indexed: 12/24/2023] Open
Abstract
Globally, Streptococcus pneumoniae is a leading cause of vaccine-preventable morbidity and mortality in infants and children. In recent decades, large-scale pediatric immunization programs have substantially reduced the incidence of invasive pneumococcal disease. Despite this, residual vaccine-type pneumococcal disease remains in the form of vaccine breakthrough and vaccine failure. This targeted literature review aims to discuss aspects of vaccine breakthrough and failure in infants and children, including disease epidemiology, clinical presentation, risk factors, vaccination schedules, vaccine serotypes, correlates of protection, comorbidities, disease surveillance, and potential implications for future vaccine development.
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Affiliation(s)
- Kristen Feemster
- Merck & Co., Inc., Rahway, NJ 07065, USA; (J.W.); (U.B.); (N.B.); (K.S.C.)
| | - Jessica Weaver
- Merck & Co., Inc., Rahway, NJ 07065, USA; (J.W.); (U.B.); (N.B.); (K.S.C.)
| | - Ulrike Buchwald
- Merck & Co., Inc., Rahway, NJ 07065, USA; (J.W.); (U.B.); (N.B.); (K.S.C.)
| | - Natalie Banniettis
- Merck & Co., Inc., Rahway, NJ 07065, USA; (J.W.); (U.B.); (N.B.); (K.S.C.)
| | - Kara S. Cox
- Merck & Co., Inc., Rahway, NJ 07065, USA; (J.W.); (U.B.); (N.B.); (K.S.C.)
| | | | - Vana Spoulou
- Immunobiology and Vaccinology Research Laboratory, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece;
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10
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Papachristidou S, Lapea V, Charisi M, Kourkouni E, Kousi D, Xirogianni A, Dedousi O, Papaconstadopoulos I, Eleftheriou E, Krepis P, Pasparaki S, Pantalos G, Doudoulakakis A, Bozavoutoglou E, Daskalaki M, Kostaridou-Nikolopoulou S, Tzanakaki G, Spoulou V, Tsolia M. A multicenter study on the epidemiology of complicated parapneumonic effusion in the era of currently available pneumococcal conjugate vaccines. Vaccine 2023; 41:6727-6733. [PMID: 37805358 DOI: 10.1016/j.vaccine.2023.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 09/27/2023] [Accepted: 10/02/2023] [Indexed: 10/09/2023]
Abstract
BACKGROUND Parapneumonic effusion (PPE) is a common complication of pneumonia. Streptococcus pneumoniae is the most common cause of bacterial pneumonia. A reduction in pneumonia hospitalizations has been observed since the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). Despite this apparent benefit, an increase in the incidence of PPE was recorded in some countries following PCV7 implementation. As the 13-valent pneumococcal conjugate vaccine (PCV13) was expected to provide a wider protection against PPE, the aim of the present study was to evaluate the impact of PCV13 introduction on the epidemiology of complicated parapneumonic effusion (c-PPE) among children in the Athens greater area. METHODS All cases of community-acquired pneumonia (CAP) with PPE requiring chest tube insertion (complicated PPE, c-PPE) hospitalized in the 3 public Children's hospitals in Athens between 01/01/2004 and 31/12/2019 were included in the study. RESULTS A total of 426 cases of c-PPE associated with pneumonia were recorded of which 198 were admitted during 2004-2010 (period A, prePCV13/PCV -7 introduction period) and 228 during 2011-2018 (period B, post - PCV13 period). A definite bacterial etiology was established in 44.4 % of all cases and of those 25.4 % were caused by S. pneumoniae. An increasing trend in c-PPE incidence was observed during period A; although, a significant decrease on c-PPE annual rates was observed during the period B (p = 0.011), a remarkable increase in serotype 3 cases was recorded. CONCLUSION A decreasing time trend in c-PPE cases among children was shown after the introduction of PCV13 in our area. However, serotype 3 is nowadays a common cause of PPE. Hence, continuous surveillance is imperative in order to follow c-PPE epidemiology over time.
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Affiliation(s)
- Smaragda Papachristidou
- Second Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), P.& A. Kyriakou Children's Hospital, Athens, Greece.
| | - Vasiliki Lapea
- First Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), Aghia Sophia Children's Hospital, Athens, Greece
| | - Martha Charisi
- Department of Paediatrics, Penteli Children's Hospital, Athens, Greece
| | - Eleni Kourkouni
- Collaborative Center for Clinical Epidemiology and Outcomes Research (CLEO), Athens, Greece
| | - Dimitra Kousi
- Collaborative Center for Clinical Epidemiology and Outcomes Research (CLEO), Athens, Greece
| | - Athanasia Xirogianni
- National Meningitis Reference Laboratory, Dept of Public Health Policy, School of Public Health, University of West Attica, Athens, Greece
| | - Olga Dedousi
- Second Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), P.& A. Kyriakou Children's Hospital, Athens, Greece
| | - Irene Papaconstadopoulos
- First Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), Aghia Sophia Children's Hospital, Athens, Greece
| | - Eirini Eleftheriou
- Second Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), P.& A. Kyriakou Children's Hospital, Athens, Greece
| | - Panagiotis Krepis
- Second Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), P.& A. Kyriakou Children's Hospital, Athens, Greece
| | - Sophia Pasparaki
- Second Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), P.& A. Kyriakou Children's Hospital, Athens, Greece
| | - Georgios Pantalos
- Pediatric Intensive Care Unit, Penteli's Children Hospital, Penteli, Greece
| | | | | | - Maria Daskalaki
- Microbiology Laboratory, Penteli Children's Hospital, Athens, Greece
| | | | - Georgina Tzanakaki
- National Meningitis Reference Laboratory, Dept of Public Health Policy, School of Public Health, University of West Attica, Athens, Greece
| | - Vana Spoulou
- First Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), Aghia Sophia Children's Hospital, Athens, Greece
| | - Maria Tsolia
- Second Department of Paediatrics, School of Medicine, National and Kapodistrian University of Athens (NKUA), P.& A. Kyriakou Children's Hospital, Athens, Greece
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11
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Martinon-Torres F, Wysocki J, Szenborn L, Carmona-Martinez A, Poder A, Dagan R, Richmond P, Gilbert C, Trudel MC, Flores S, Lupinacci R, McFetridge R, Wiedmann RT, Chen Q, Gerrits H, Banniettis N, Musey L, Bickham K, Kaminski J. A Phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of V114 compared with PCV13 in healthy infants (PNEU-PED-EU-1). Vaccine 2023; 41:3387-3398. [PMID: 37105892 DOI: 10.1016/j.vaccine.2023.04.036] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 04/05/2023] [Accepted: 04/11/2023] [Indexed: 04/29/2023]
Abstract
BACKGROUND V114 (15-valent pneumococcal conjugate vaccine [PCV]) contains all serotypes in 13-valent PCV (PCV13) and additional serotypes 22F and 33F. This study evaluated safety and immunogenicity of V114 compared with PCV13 in healthy infants, and concomitant administration with DTPa-HBV-IPV/Hib and rotavirus RV1 vaccines. METHODS V114 and PCV13 were administered in a 2+1 schedule at 2, 4, and 11-15 months of age. Adverse events (AEs) were collected on Days 1-14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series (PPS), immediately prior to a toddler dose, and 30 days post-toddler dose (PTD). Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for the two additional serotypes. RESULTS 1184 healthy infants 42-90 days of age were randomized 1:1 to V114 (n = 591) or PCV13 (n = 593). Proportions of participants with solicited AEs and serious AEs were comparable between vaccination groups. V114 met pre-specified non-inferiority criteria for all 13 shared serotypes, based on the difference in proportions of participants with serotype-specific IgG concentrations ≥0.35 μg/mL (response rate; lower bound of two-sided 95% confidence interval [CI] >-10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5), and pre-specified superiority criteria for serotypes 22F and 33F (lower bound of two-sided 95% CI >10.0 for response rates and >2.0 for GMC ratios). Antibody responses to DTPa-HBV-IPV/Hib and RV1 vaccines met pre-specified non-inferiority criteria, based on antigen-specific response rates to DTPa-HBV-IPV/Hib and anti-rotavirus IgA geometric mean titers. CONCLUSIONS After a 2+1 schedule, V114 elicited non-inferior immune responses to 13 shared serotypes and superior responses to the two additional serotypes compared with PCV13, with comparable safety profile. These results support the routine use of V114 in infants. TRIAL REGISTRATION ClinicalTrials.gov: NCT04031846; EudraCT: 2018-003787-31.
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Affiliation(s)
- Federico Martinon-Torres
- Translational Pediatrics and Infectious Diseases, Pediatrics Department, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Genetics, Vaccines and Infections Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago, University of Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
| | | | | | | | - Airi Poder
- Clinical Research Center, Tartu, Estonia
| | - Ron Dagan
- The Shraga Segal Dept. of Microbiology, Immunology and Genetics, Faculty of Health Sciences of the Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Peter Richmond
- Telethon Kids Institute and School of Medicine, The University of Western Australia, Crawley, WA 6009, Australia
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12
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Alford MA, Karlowsky JA, Adam HJ, Baxter MR, Schellenberg J, Golden AR, Martin I, Demczuk W, Mulvey MR, Zhanel GG. Antimicrobial susceptibility testing of invasive isolates of Streptococcus pneumoniae from Canadian patients: the SAVE study, 2011-2020. J Antimicrob Chemother 2023; 78:i8-i16. [PMID: 37130584 DOI: 10.1093/jac/dkad065] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/04/2023] Open
Abstract
OBJECTIVES To assess the antimicrobial susceptibility of 14 138 invasive Streptococcus pneumoniae isolates collected in Canada from 2011 to 2020. METHODS Antimicrobial susceptibility testing was performed using the CLSI M07 broth microdilution reference method. MICs were interpreted using 2022 CLSI M100 breakpoints. RESULTS In 2020, 90.1% and 98.6% of invasive pneumococci were penicillin-susceptible when MICs were interpreted using CLSI meningitis or oral and non-meningitis breakpoints, respectively; 96.9% (meningitis breakpoint) and 99.5% (non-meningitis breakpoint) of isolates were ceftriaxone-susceptible, and 99.9% were levofloxacin-susceptible. Numerically small, non-temporal, but statistically significant differences (P < 0.05) in the annual percentage of isolates susceptible to four of the 13 agents tested was observed across the 10-year study: chloramphenicol (4.4% difference), trimethoprim-sulfamethoxazole (3.9%), penicillin (non-meningitis breakpoint, 2.7%) and ceftriaxone (meningitis breakpoint, 2.7%; non-meningitis breakpoint, 1.2%). During the same period, annual differences in percent susceptible values for penicillin (meningitis and oral breakpoints) and all other agents did not achieve statistical significance. The percentage of isolates with an MDR phenotype (resistance to ≥3 antimicrobial classes) in 2011 and 2020 (8.5% and 9.4%) was not significantly different (P = 0.109), although there was a significant interim decrease observed between 2011 and 2015 (P < 0.001) followed by a significant increase between 2016 and 2020 (P < 0.001). Statistically significant associations were observed between resistance rates to most antimicrobial agents included in the MDR analysis (penicillin, clarithromycin, clindamycin, doxycycline, trimethoprim/sulfamethoxazole and chloramphenicol) and patient age, specimen source, geographic location in Canada or concurrent resistance to penicillin or clarithromycin, but not biological sex of patients. Given the large isolate collection studied, statistical significance did not necessarily imply clinical or public health significance in some analyses. CONCLUSIONS Invasive pneumococcal isolates collected in Canada from 2011 to 2020 generally exhibited consistent in vitro susceptibility to commonly tested antimicrobial agents.
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Affiliation(s)
- Morgan A Alford
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
| | - James A Karlowsky
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
- Clinical Microbiology, Shared Health, MS673-820 Sherbrook Street, Winnipeg, Manitoba R3A 1R9, Canada
| | - Heather J Adam
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
- Clinical Microbiology, Shared Health, MS673-820 Sherbrook Street, Winnipeg, Manitoba R3A 1R9, Canada
| | - Melanie R Baxter
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
| | - John Schellenberg
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
| | - Alyssa R Golden
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3M4, Canada
| | - Irene Martin
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3M4, Canada
| | - Walter Demczuk
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3M4, Canada
| | - Michael R Mulvey
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba R3E 3M4, Canada
| | - George G Zhanel
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Room 543-745 Bannatyne Avenue, Winnipeg, Manitoba R3E 0J9, Canada
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13
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Downs SL, Madhi SA, van der Merwe L, Nunes MC, Olwagen CP. Optimization of a high-throughput nanofluidic real-time PCR to detect and quantify of 15 bacterial species and 92 Streptococcus pneumoniae serotypes. Sci Rep 2023; 13:4588. [PMID: 36944704 PMCID: PMC10030628 DOI: 10.1038/s41598-023-31820-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 03/17/2023] [Indexed: 03/23/2023] Open
Abstract
Sensitive tools for detecting concurrent colonizing pneumococcal serotypes are needed for detailed evaluation of the direct and indirect impact of routine pneumococcal conjugate vaccine (PCV) immunization. A high-throughput quantitative nanofluidic real-time PCR (Standard BioTools 'Fluidigm') reaction-set was developed to detect and quantify 92 pneumococcal serotypes in archived clinical samples. Nasopharyngeal swabs collected in 2009-2011 from South African children ≤ 5 years-old, previously serotyped with standard culture-based methods were used for comparison. The reaction-set within the 'Fluidigm' effectively amplified all targets with high efficiency (90-110%), reproducibility (R2 ≥ 0.98), and at low limit-of-detection (< 102 CFU/ml). A blind analysis of 1 973 nasopharyngeal swab samples showed diagnostic sensitivity > 80% and specificity > 95% compared with the referent standard, culture based Quellung method. The qPCR method was able to serotype pneumococcal types with good discrimination compared with Quellung (ROC-AUC: > 0.73). The high-throughput nanofluidic real-time PCR method simultaneously detects 57 individual serotypes, and 35 serotypes within 16 serogroups in 96 samples (including controls), within a single qPCR run. This method can be used to evaluate the impact of current PCV formulations on vaccine-serotype and non-vaccine-serotype colonization, including detection of multiple concurrently colonizing serotypes. Our qPCR method can allow for monitoring of serotype-specific bacterial load, as well as emergence or ongoing transmission of minor or co-colonizing serotypes that may have invasive disease potential.
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Affiliation(s)
- Sarah L Downs
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
| | - Shabir A Madhi
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Lara van der Merwe
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Marta C Nunes
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Courtney P Olwagen
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
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14
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Lupinacci R, Rupp R, Wittawatmongkol O, Jones J, Quinones J, Ulukol B, Dagan R, Richmond P, Stek JE, Romero L, Koseoglu S, Tamms G, McFetridge R, Li J, Cheon K, Musey L, Banniettis N, Bickham K. A phase 3, multicenter, randomized, double-blind, active-comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of a 4-dose regimen of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants (PNEU-PED). Vaccine 2023; 41:1142-1152. [PMID: 36621410 DOI: 10.1016/j.vaccine.2022.12.054] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 12/19/2022] [Accepted: 12/20/2022] [Indexed: 01/09/2023]
Abstract
BACKGROUND Pneumococcal disease (PD) remains a major health concern with considerable morbidity and mortality in children. Currently licensed pneumococcal conjugate vaccines (PCVs) confer protection against PD caused by most vaccine serotypes, but non-vaccine serotypes contribute to residual disease. V114 is a 15-valent PCV containing all 13 serotypes in Prevnar 13™ (PCV13) and additional serotypes 22F and 33F. This pivotal phase 3 study compared safety and immunogenicity of V114 and PCV13. METHODS 1720 healthy infants were randomized 1:1 to receive a 4-dose regimen of V114 or PCV13 concomitantly with other routine pediatric vaccines. Safety was evaluated after each dose as proportion of participants with adverse events (AEs). Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured at 1-month post-dose 3 (PD3), pre-dose 4, and 1-month post-dose 4 (PD4). IgG response rates, geometric mean concentrations (GMCs), and opsonophagocytic activity (OPA) were compared between vaccination groups. RESULTS The proportion, maximum intensity, and duration of injection-site, systemic, and serious AEs were generally comparable between V114 and PCV13 groups. In comparison to PCV13, V114 met non-inferiority criteria for all 15 serotypes based on IgG response rates at PD3. V114 met non-inferiority criteria by IgG GMCs for all serotypes at PD3 and PD4, except for serotype 6A at PD3. V114-induced antibodies had bactericidal activity as assessed by OPA. Further, V114 met superiority criteria for shared serotype 3 and unique serotypes 22F and 33F compared to PCV13 by serotype-specific IgG GMCs at both PD3 and PD4. Immunogenicity of concomitantly administered routine pediatric vaccines was comparable in V114 and PCV13 groups. CONCLUSIONS In healthy infants, V114 displays acceptable safety and tolerability profiles and generates comparable immune responses to PCV13. V114 also met superiority criteria for serotypes 3, 22F, and 33F. These results support use of V114 for prevention of PD as part of routine infant vaccination schedules. TRIAL REGISTRATION ClinicalTrials.gov: NCT03893448; EudraCT: 2018-004109-21.
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Affiliation(s)
| | - Richard Rupp
- University of Texas Medical Branch, Galveston, TX, USA
| | | | | | | | | | - Ron Dagan
- The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences of the Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Peter Richmond
- University of Western Australia School of Medicine, Perth, Australia
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15
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Bili A, Dobson S, Quinones J, Phongsamart W, Oberdorfer P, Kosalaraksa P, Dagan R, Richmond P, Wilck M, Vallejos W, Nunn C, McFetridge R, Tamms G, Fu R, Lupinacci R, Musey L, Banniettis N, Bickham K. A phase 3, multicenter, randomized, double-blind study to evaluate the interchangeability of V114, a 15-valent pneumococcal conjugate vaccine, and PCV13 with respect to safety, tolerability, and immunogenicity in healthy infants (PNEU-DIRECTION). Vaccine 2023; 41:657-665. [PMID: 36522265 DOI: 10.1016/j.vaccine.2022.10.072] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 10/24/2022] [Accepted: 10/26/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Pneumococcal disease (PD) remains a major health concern globally. In children, pneumococcal conjugate vaccines (PCVs) provide protection against PD from most vaccine serotypes, but non-vaccine serotypes contribute to residual disease. V114 is a 15-valent PCV containing all 13 serotypes in Prevnar 13™ (PCV13) and public health important serotypes 22F and 33F. This phase 3 study evaluated safety and immunogenicity of mixed PCV13/V114 regimens using a 3 + 1 dosing schedule when changing from PCV13 to V114 at doses 2, 3, or 4. METHODS 900 healthy infants were randomized equally to 5 intervention groups. PCVs were administered in a 3-dose infant series at 2, 4, and 6 months of age followed by a toddler dose at 12-15 months along with concomitant routine vaccines. Safety was evaluated as the proportion of participants with adverse events (AEs). Immunoglobulin G (IgG) responses to the 15 serotypes in V114 were measured at 30 days post-dose 3 and 30 days post-dose 4 (PD4). RESULTS Frequencies of injection-site and systemic AEs were generally comparable across all intervention groups. At 30 days PD4 (primary endpoint), IgG geometric mean concentrations (GMCs) for the 13 shared serotypes were generally comparable between mixed V114/PCV13 and 4-dose regimens of PCV13 or V114. In mixed regimens at 30 days PD4, a toddler dose of V114 was sufficient to achieve IgG GMCs comparable to a 4-dose regimen of V114 for serotype 22F, while at least one infant dose was needed in addition to the toddler dose to achieve IgG GMCs comparable to a 4-dose regimen of V114 for serotype 33F. CONCLUSIONS V114 was well tolerated with a generally comparable safety profile to PCV13. For 13 shared serotypes, both mixed regimens and the V114 4-dose regimen induced generally comparable antibody responses to 4-dose regimen with PCV13. Study results support interchangeability of V114 with PCV13 in infants. TRIAL REGISTRATION ClinicalTrials.gov: NCT03620162; EudraCT: 2018-001151-12.
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Affiliation(s)
| | - Scott Dobson
- Parkside Clinical Research and Tribe Clinical Research, Greenville, SC, USA
| | | | | | | | | | - Ron Dagan
- The Shraga Segal Dept. of Microbiology, Immunology and Genetics, Faculty of Health Sciences of the Ben-Gurion University of the Negev Beer-Sheva, Israel
| | - Peter Richmond
- University of Western Australia School of Medicine, Perth, Australia
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16
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Ordóñez JE, Ordóñez A. A cost-effectiveness analysis of pneumococcal conjugate vaccines in infants and herd protection in older adults in Colombia. Expert Rev Vaccines 2023; 22:216-225. [PMID: 36812426 DOI: 10.1080/14760584.2023.2184090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
BACKGROUND Pneumococcal diseases have a clinical and economic impact on the population. Until this year, a 10-valent pneumococcal vaccine (PCV10) used to be applied in Colombia, which does not contain serotypes 19A, 3, and 6A, the most prevalent in the country. Therefore, we aimed to assess the cost-effectiveness of the shift to the 13-valent pneumococcal vaccine (PCV13). RESEARCH DESIGN AND METHODS A decision model was used for newborns in Colombia between 2022-2025 and adults over 65 years. The time horizon was life expectancy. Outcomes are Invasive Pneumococcal Diseases (IPD), Community-Acquired Pneumonia (CAP), Acute Otitis Media (AOM), their sequelae, Life Gained Years (LYGs), and herd effect in older adults. RESULTS PCV10 covers 4.27% of serotypes in the country, while PCV13 covers 64.4%. PCV13 would avoid in children 796 cases of IPD, 19,365 of CAP, 1,399 deaths, and generate 44,204 additional LYGs, as well as 9,101 cases of AOM, 13 cases of neuromotor disability and 428 cochlear implants versus PCV10. In older adults, PCV13 would avoid 993 cases of IPD and 17,245 of CAP, versus PCV10. PCV13 saves $51.4 million. The decision model shows robustness in the sensitivity analysis. CONCLUSION PCV13 is a cost-saving strategy versus PCV10 to avoid pneumococcal diseases.
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Affiliation(s)
| | - Angélica Ordóñez
- Instituto de Evaluación Tecnológica en Salud, Bogotá, D.C, Colombia
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Changes in Etiology of Invasive Bacterial Infections in Infants Under 3 Months of Age in Korea, 2006-2020. Pediatr Infect Dis J 2022; 41:941-946. [PMID: 36375095 DOI: 10.1097/inf.0000000000003714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVES Invasive bacterial infection (IBI) causes a significant burden in infants. In this study, we analyzed changes in epidemiology of IBI among infants in Korea. METHODS A retrospective multicenter-based surveillance for IBIs in infants <3 months of age was performed during 2006-2020. Cases were classified as an early-onset disease (EOD) (0-6 days) or late-onset disease (LOD) (7-89 days). The temporal trend change in proportion of pathogens was analyzed. RESULTS Among 1545 cases, the median age was 28 days (IQR: 12, 53) and EOD accounted for 17.7%. Among pathogens, S. agalactiae (40.4%), E. coli (38.5%), and S. aureus (17.8%) were the most common and attributed for 96.7%. Among EOD (n = 274), S. agalactiae (45.6%), S. aureus (31.4%), E. coli (17.2%) and L. monocytogenes (2.9%) were most common. Among LOD (n = 1274), E. coli (43.1%), S. agalactiae (39.3%), S. aureus (14.9%) and S. pneumoniae (1.3%) were most common. In the trend analysis, the proportion of S. aureus (r s = -0.850, P < 0.01) decreased significantly, while that of S. agalactiae increased (r s = 0.781, P < 0.01). CONCLUSION During 2006-2020, among IBI in infants <3 months of age, S. agalactiae, E. coli, and S. aureus were most common and an increasing trend of S. agalactiae was observed.
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Koenraads M, Swarthout TD, Bar-Zeev N, Brown C, Msefula J, Denis B, Dube Q, Gordon SB, Heyderman RS, Gladstone MJ, French N. Changing Incidence of Invasive Pneumococcal Disease in Infants Less Than 90 Days of Age Before and After Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Blantyre, Malawi: A 14-Year Hospital Based Surveillance Study. Pediatr Infect Dis J 2022; 41:764-768. [PMID: 35703302 PMCID: PMC9359774 DOI: 10.1097/inf.0000000000003606] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/06/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND Invasive pneumococcal disease (IPD) in young infants is uncommon but associated with high morbidity and mortality. Accurate data on the burden of IPD in young infants in low-income countries are lacking. We examined the burden of IPD in infants <90 days old in Blantyre, Malawi over a 14-year period and evaluated the indirect impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on vaccine-serotype IPD (VT-IPD) in this population. METHODS We conducted laboratory-based prospective IPD surveillance in infants <90 days of age admitted to Queen Elizabeth Central Hospital in Blantyre between 2005 and 2018, including 7 years pre-PCV13 and 7 years post-PCV13 introduction. IPD was defined as Streptococcus pneumoniae identified by culture from blood or cerebrospinal fluid. Serotypes were determined by multiplex polymerase chain reaction and latex agglutination testing. RESULTS We identified 130 cases of culture-confirmed IPD in infants <90 days old between 2005 and 2018. Total IPD incidence was declining before PCV13 introduction. The mean incidence of IPD was significantly lower in the post-PCV13 era. Serotypes 5 (27.8%) and 1 (15.6%) were most prevalent. Even after PCV13 introduction, VTs remained the primary cause of IPD, with serotype 5 accounting for 17.4% and serotype 1 for 13.0% of cases in young infants. CONCLUSION Vaccine serotypes 1 and 5 were the main cause of IPD in neonates and young infants, both before and after PCV13 introduction. This suggests incomplete indirect protection with persisting VT carriage across the population despite vaccination in this setting. Alternative vaccine schedules and other vaccine introduction approaches need to be considered to protect this vulnerable population.
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Affiliation(s)
- Marianne Koenraads
- From the Department of Women and Children’s Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
| | - Todd D. Swarthout
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi
- NIHR Global Health Research Unit on Mucosal Pathogens, Research Department of Infection, Division of Infection and Immunity, University College London, London, United Kingdom
| | - Naor Bar-Zeev
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi
- Department of Clinical Infection, Microbiology and Immunology, Institute of Infection Veterinary and Ecological Science, University of Liverpool, Liverpool, United Kingdom
- International Vaccine Access Center, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States
| | - Comfort Brown
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi
| | - Jacquline Msefula
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi
| | - Brigitte Denis
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi
| | - Queen Dube
- Department of Paediatrics, Kamuzu University of Health Sciences, Blantyre, Malawi
| | - Stephen B. Gordon
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi
- Liverpool School of Tropical Medicine, Liverpool, United Kingdom
| | - Robert S. Heyderman
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi
- NIHR Global Health Research Unit on Mucosal Pathogens, Research Department of Infection, Division of Infection and Immunity, University College London, London, United Kingdom
| | - Melissa J. Gladstone
- From the Department of Women and Children’s Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
| | - Neil French
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Kamuzu University of Health Sciences, Blantyre, Malawi
- Department of Clinical Infection, Microbiology and Immunology, Institute of Infection Veterinary and Ecological Science, University of Liverpool, Liverpool, United Kingdom
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Annual Trend in Lumbar Puncture for Infants Younger Than 3 Months Hospitalized With Suspected Serious Bacterial Infection: A Nationwide Inpatient Database Study. Pediatr Infect Dis J 2022; 41:631-635. [PMID: 35544737 DOI: 10.1097/inf.0000000000003572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND A lumbar puncture is no longer necessary in febrile infants younger than 3 months when they are at low risk of serious bacterial infection because the risk factors for a severe bacterial infection have been identified. The purpose of this study was to identify the annual trend in the proportion of lumbar punctures in infants with suspected serious bacterial infections using a national inpatient database in Japan. METHODS Using the Diagnosis Procedure Combination database, we identified infants < 3 months of age who underwent blood and urine culture tests on admission from April 2011 to March 2020 in Japan. RESULTS In total, 44,910 eligible infants were included in the study. The proportion of lumbar punctures decreased gradually from 57.9% to 50.4% in infants 4-28 days old and from 54.5% to 37.3% in infants 29-89 days old between 2011 and 2019. Of the 18 hospitals, 15 (83.3%) recorded a lumbar puncture proportion of >50% in 2011 and 7 (38.9%) recorded >50% in 2019. In 3 hospitals, the proportion of lumbar punctures remained >75% in 2019. CONCLUSION The proportion of lumbar punctures with hospitalized infants admitted with blood and urine culture tests decreased over the years, and this trend was greater in infants 29-89 days of age. The reduction in the proportion of lumbar punctures varied widely among the hospitals.
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Kremer PHC, Ferwerda B, Bootsma HJ, Rots NY, Wijmenga-Monsuur AJ, Sanders EAM, Trzciński K, Wyllie AL, Turner P, van der Ende A, Brouwer MC, Bentley SD, van de Beek D, Lees JA. Pneumococcal genetic variability in age-dependent bacterial carriage. eLife 2022; 11:e69244. [PMID: 35881438 PMCID: PMC9395192 DOI: 10.7554/elife.69244] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 07/03/2022] [Indexed: 11/13/2022] Open
Abstract
The characteristics of pneumococcal carriage vary between infants and adults. Host immune factors have been shown to contribute to these age-specific differences, but the role of pathogen sequence variation is currently less well-known. Identification of age-associated pathogen genetic factors could leadto improved vaccine formulations. We therefore performed genome sequencing in a large carriage cohort of children and adults and combined this with data from an existing age-stratified carriage study. We compiled a dictionary of pathogen genetic variation, including serotype, strain, sequence elements, single-nucleotide polymorphisms (SNPs), and clusters of orthologous genes (COGs) for each cohort - all of which were used in a genome-wide association with host age. Age-dependent colonization showed weak evidence of being heritable in the first cohort (h2 = 0.10, 95% CI 0.00-0.69) and stronger evidence in the second cohort (h2 = 0.56, 95% CI 0.23-0.87). We found that serotypes and genetic background (strain) explained a proportion of the heritability in the first cohort (h2serotype = 0.07, 95% CI 0.04-0.14 and h2GPSC = 0.06, 95% CI 0.03-0.13) and the second cohort (h2serotype = 0.11, 95% CI 0.05-0.21 and h2GPSC = 0.20, 95% CI 0.12-0.31). In a meta-analysis of these cohorts, we found one candidate association (p=1.2 × 10-9) upstream of an accessory Sec-dependent serine-rich glycoprotein adhesin. Overall, while we did find a small effect of pathogen genome variation on pneumococcal carriage between child and adult hosts, this was variable between populations and does not appear to be caused by strong effects of individual genes. This supports proposals for adaptive future vaccination strategies that are primarily targeted at dominant circulating serotypes and tailored to the composition of the pathogen populations.
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Affiliation(s)
- Philip HC Kremer
- Department of Neurology, Amsterdam UMC, University of AmsterdamMeibergdreefNetherlands
| | - Bart Ferwerda
- Department of Neurology, Amsterdam UMC, University of AmsterdamMeibergdreefNetherlands
- Department of Clinical Epidemiology, Biostatistics and Bioinformatics, University of AmsterdamAmsterdamNetherlands
| | - Hester J Bootsma
- Centre for Infectious Disease Control, National Institute for Public Health and the EnvironmentBilthovenNetherlands
| | - Nienke Y Rots
- Centre for Infectious Disease Control, National Institute for Public Health and the EnvironmentBilthovenNetherlands
| | - Alienke J Wijmenga-Monsuur
- Centre for Infectious Disease Control, National Institute for Public Health and the EnvironmentBilthovenNetherlands
| | - Elisabeth AM Sanders
- Centre for Infectious Disease Control, National Institute for Public Health and the EnvironmentBilthovenNetherlands
- Department of Pediatric Immunology and Infectious D, Wilhelmina Children's HospitalUtrechtNetherlands
| | - Krzysztof Trzciński
- Department of Pediatric Immunology and Infectious D, Wilhelmina Children's HospitalUtrechtNetherlands
| | - Anne L Wyllie
- Department of Pediatric Immunology and Infectious D, Wilhelmina Children's HospitalUtrechtNetherlands
- Epidemiology of Microbial Diseases, Yale School of Public HealthNew HavenUnited States
| | - Paul Turner
- Cambodia Oxford Medical Research Unit, Angkor Hospital for ChildrenSiem ReapCambodia
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of OxfordOxfordUnited Kingdom
| | - Arie van der Ende
- Department of Medical Microbiology and Infection Prevention, Amsterdam UMCAmsterdamNetherlands
- The Netherlands Reference Laboratory for Bacterial MeningitisAmsterdamNetherlands
| | - Matthijs C Brouwer
- Department of Neurology, Amsterdam UMC, University of AmsterdamMeibergdreefNetherlands
| | - Stephen D Bentley
- Parasites and Microbes, Wellcome Sanger InstituteCambridgeUnited Kingdom
| | - Diederik van de Beek
- Department of Neurology, Amsterdam UMC, University of AmsterdamMeibergdreefNetherlands
| | - John A Lees
- European Molecular Biology Laboratory–European Bioinformatics InstituteCambridgeUnited Kingdom
- MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College LondonLondonUnited Kingdom
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Hsiao A, Hansen J, Timbol J, Lewis N, Isturiz R, Alexander-Parrish R, McLaughlin JM, Gessner BD, Klein NP. Incidence and Estimated Vaccine Effectiveness Against Hospitalizations for All-Cause Pneumonia Among Older US Adults Who Were Vaccinated and Not Vaccinated With 13-Valent Pneumococcal Conjugate Vaccine. JAMA Netw Open 2022; 5:e221111. [PMID: 35302634 PMCID: PMC8933738 DOI: 10.1001/jamanetworkopen.2022.1111] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 01/17/2022] [Indexed: 12/22/2022] Open
Abstract
Importance Following routine use of 13-valent pneumococcal conjugate vaccine (PCV13) in children in 2010, invasive pneumococcal disease rates have decreased substantially in children and adults. In 2014, the Advisory Committee for Immunization Practices recommended routine use of PCV13 among adults aged 65 years or older; previously only 23-valent pneumococcal polysaccharide vaccine (PPV23) was recommended. Objective To estimate the association between the incidence of hospitalized all-cause pneumonia and lower respiratory tract infections (LRTI) and PCV13 vaccination among older adults at Kaiser Permanente Northern California (KPNC). Design, Setting, and Participants This retrospective cohort study included adults at KPNC aged 65 years or older between July 1, 2015, and June 30, 2018, born after 1936 with no known history of PPV23 or PCV13 receipt before age 65. The study took place at an integrated health care system with an annual membership more than 4 million individuals, approximately 15% of whom are 65 years or older and broadly representative of the region. Data analysis took place from July 2018 to December 2021, and data collection took place from November 2016 to June 2018. Exposures PCV13 vaccination status was ascertained from the electronic medical record (EMR). Individuals were considered vaccinated 14 days following immunization. Main Outcomes and Measures First hospitalized all-cause pneumonia was identified in the EMR using primary/secondary discharge diagnosis International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. First hospitalized LRTI was identified using pneumonia codes and acute bronchitis codes. Relative risk (RR) of first pneumonia or LRTI hospitalization of individuals who were PCV13 vaccinated vs PCV13 unvaccinated was estimated using Poisson regressions adjusted for sex, race, ethnicity, age, influenza vaccine receipt, PPV23 receipt since age 65, pneumonia risk factors, health care use, and season. Vaccine effectiveness (VE) was estimated as (1-RR) × 100%. Results Of 192 061 adults, 107 957 (56%) were female and 139 024 (72%) were White individuals. PCV13 coverage increased from 0 in 2014 to 135 608 (76.9%) by 2018. There were 3488 individuals with 3766 pneumonia hospitalizations and 3846 individuals with 4173 LRTI hospitalizations. PCV13 was associated with an adjusted VE of 10.0% (95% CI, 2.4-17.0; P = .01) against hospitalized pneumonia and 9.4% (95% CI, 2.1-16.1; P = .01) against hospitalized LRTI. Conclusions and Relevance In the context of a robust pediatric PCV13 immunization program, PCV13 vaccination of adults aged 65 years or older was associated with significant reductions in hospitalizations for all-cause pneumonia and LRTI. Vaccinating older adults with PCVs may provide broader public health benefit against pneumonia hospitalizations.
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Affiliation(s)
- Amber Hsiao
- Kaiser Permanente Vaccine Study Center, Oakland, California
| | - John Hansen
- Kaiser Permanente Vaccine Study Center, Oakland, California
| | - Julius Timbol
- Kaiser Permanente Vaccine Study Center, Oakland, California
| | - Ned Lewis
- Kaiser Permanente Vaccine Study Center, Oakland, California
| | - Raul Isturiz
- Pfizer Vaccine Medicines Development and Scientific Clinical Affairs, Collegeville, Pennsylvania
| | - Ronika Alexander-Parrish
- Pfizer Vaccine Medicines Development and Scientific Clinical Affairs, Collegeville, Pennsylvania
| | - John M. McLaughlin
- Pfizer Vaccine Medicines Development and Scientific Clinical Affairs, Collegeville, Pennsylvania
| | - Bradford D. Gessner
- Pfizer Vaccine Medicines Development and Scientific Clinical Affairs, Collegeville, Pennsylvania
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22
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Gingerich AD, Mousa JJ. Diverse Mechanisms of Protective Anti-Pneumococcal Antibodies. Front Cell Infect Microbiol 2022; 12:824788. [PMID: 35155281 PMCID: PMC8834882 DOI: 10.3389/fcimb.2022.824788] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 01/11/2022] [Indexed: 02/05/2023] Open
Abstract
The gram-positive bacterium Streptococcus pneumoniae is a leading cause of pneumonia, otitis media, septicemia, and meningitis in children and adults. Current prevention and treatment efforts are primarily pneumococcal conjugate vaccines that target the bacterial capsule polysaccharide, as well as antibiotics for pathogen clearance. While these methods have been enormously effective at disease prevention and treatment, there has been an emergence of non-vaccine serotypes, termed serotype replacement, and increasing antibiotic resistance among these serotypes. To combat S. pneumoniae, the immune system must deploy an arsenal of antimicrobial functions. However, S. pneumoniae has evolved a repertoire of evasion techniques and is able to modulate the host immune system. Antibodies are a key component of pneumococcal immunity, targeting both the capsule polysaccharide and protein antigens on the surface of the bacterium. These antibodies have been shown to play a variety of roles including increasing opsonophagocytic activity, enzymatic and toxin neutralization, reducing bacterial adherence, and altering bacterial gene expression. In this review, we describe targets of anti-pneumococcal antibodies and describe antibody functions and effectiveness against S. pneumoniae.
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Affiliation(s)
- Aaron D. Gingerich
- Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, United States
| | - Jarrod J. Mousa
- Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, United States
- Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United States
- Department of Biochemistry and Molecular Biology, Franklin College of Arts and Sciences, University of Georgia, Athens, GA, United States
- *Correspondence: Jarrod J. Mousa,
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23
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Deen J, Clemens JD. Assessment of Vaccine Herd Protection: Lessons Learned From Cholera and Typhoid Vaccine Trials. J Infect Dis 2021; 224:S764-S769. [PMID: 34273168 PMCID: PMC8687079 DOI: 10.1093/infdis/jiab358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Vaccine herd protection is the extension of the defense conferred by immunization beyond the vaccinated to unvaccinated persons in a population, as well as the enhancement of the protection among the vaccinated, due to vaccination of the surrounding population. Vaccine herd protection has traditionally been inferred from observations of disease trends after inclusion of a vaccine in national immunization schedules. Rather than awaiting outcomes of widescale vaccine deployment, earlier-stage evaluation of vaccine herd protection during trials or mass vaccination projects could help inform policy decisions about potential vaccine introduction. We describe the components, influencing factors, and implications of vaccine herd protection and discuss various methods for assessing herd protection, using examples from cholera and typhoid vaccine studies.
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Affiliation(s)
- Jacqueline Deen
- Institute of Child Health and Human Development, National Institutes of Health, University of the Philippines, Manila, Philippines
| | - John D Clemens
- International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
- Fielding School of Public Health, University of California Los Angeles, Los Angeles, California, USA
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24
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Raghavan VR, Porter JJ, Neuman MI, Lyons TW. Trends in Management of Simple Febrile Seizures at US Children's Hospitals. Pediatrics 2021; 148:peds.2021-051517. [PMID: 34670823 DOI: 10.1542/peds.2021-051517] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/09/2021] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVE We sought to measure trends in evaluation and management of children with simple febrile seizures (SFSs) before and after the American Academy of Pediatrics updated guidelines published in 2011. METHODS In this retrospective, cross-sectional analysis, we used the Pediatric Health Information System database comprising 49 tertiary care pediatric hospitals in the United States from 2005 to 2019. We included children aged 6 to 60 months with an emergency department visit for first SFS identified using codes from the International Classification of Diseases, Ninth Revision, and International Classification of Diseases 10th Revision. RESULTS We identified 142 121 children (median age 21 months, 42.4% female) with an emergency department visit for SFS. A total of 49 668 (35.0%) children presented before and 92 453 (65.1%) after the guideline. The rate of lumbar puncture for all ages declined from 11.6% (95% confidence interval [CI], 10.8% to 12.4%) in 2005 to 0.6% (95% CI, 0.5% to 0.8%) in 2019 (P < .001). Similar reductions were noted in rates of head computed tomography (10.6% to 1.6%; P < .001), complete blood cell count (38.8% to 10.9%; P < .001), hospital admission (19.2% to 5.2%; P < .001), and mean costs ($1523 to $601; P < .001). Reductions in all outcomes began before, and continued after, the publication of the American Academy of Pediatrics guideline. There was no significant change in delayed diagnosis of bacterial meningitis (preperiod 2 of 49 668 [0.0040%; 95% CI, 0.00049% to 0.015%], postperiod 3 of 92 453 [0.0032%; 95% CI, 0.00066% to 0.0094%]; P = .99). CONCLUSIONS Diagnostic testing, hospital admission, and costs decreased over the study period, without a concomitant increase in delayed diagnosis of bacterial meningitis. These data suggest most children with SFSs can be safely managed without lumber puncture or other diagnostic testing.
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Affiliation(s)
- Vidya R Raghavan
- Division of Emergency Medicine, Boston Children's Hospital and Harvard Medical School, Harvard University, Boston, Massachusetts
| | - John J Porter
- Division of Emergency Medicine, Boston Children's Hospital and Harvard Medical School, Harvard University, Boston, Massachusetts
| | - Mark I Neuman
- Division of Emergency Medicine, Boston Children's Hospital and Harvard Medical School, Harvard University, Boston, Massachusetts
| | - Todd W Lyons
- Division of Emergency Medicine, Boston Children's Hospital and Harvard Medical School, Harvard University, Boston, Massachusetts
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25
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Fuji N, Pichichero ME, Kaur R. Comparison of specific in-vitro virulence gene expression and innate host response in locally invasive vs colonizer strains of Streptococcus pneumoniae. Med Microbiol Immunol 2021; 210:111-120. [PMID: 33751214 DOI: 10.1007/s00430-021-00701-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 02/27/2021] [Indexed: 10/21/2022]
Abstract
Among Rochester NY children, a dramatic increase in nasopharyngeal (NP) colonization by non-vaccine pneumococcal serotypes 35B and 15A occurred during years 2010-2015, after introduction of 13-valent pneumococcal conjugate vaccine (PCV13). In our population, serotype 35B strains colonized in the nasopharynx (NP) but infrequently caused acute otitis media (AOM) whereas serotype 15A strains displayed virulence, evidenced by causing AOM. To explain the virulence difference, virulence genes expression between 35B and 15A, as well as the host's immune response during asymptomatic colonization were analyzed. We investigated differences in regulation of 19 virulence genes for differences in virulence using RT-PCR in 20 35B and 14 15A strains and measured gene expression of 9 host innate cytokines in the NP to assess the mucosal inflammatory response during asymptomatic colonization. Comparing 35B versus 15A strains, genes for competence ComA and RrgC were upregulated; capsular (Cps2D) and virulence genes (PfbA, PcpA and PhtE) were downregulated among 35B strains. PavB, LytA, LytB, NanA, CiaR, PhtD, LuxS, PspA and pneumolysin (Ply) showed no difference. IL17 and IL23 gene expression were > tenfold higher during 35B compared to 15A strain asymptomatic colonization. Only IL23 showed significant difference. In the first 5 years after introduction of PCV13, serotype 35B strains emerged as asymptomatic colonizers and 15A strains emerged to cause AOM in young children. Various genes (PfbA, PcpA, Cps2D and PhtE) among tested in this analysis were downregulated in 35B whereas ComA and RrgC were significantly upregulated. For the host's cytokine response, IL23 proinflammatory response which is essential for the differentiation of Th17 lymphocytes in the NP of children with 35B strains was significantly higher than the response to 15A during asymptomatic colonization.
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Affiliation(s)
- Naoko Fuji
- Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, Rochester General Hospital, 1425 Portland Avenue, Rochester, NY, 14621, USA
| | - Michael E Pichichero
- Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, Rochester General Hospital, 1425 Portland Avenue, Rochester, NY, 14621, USA
| | - Ravinder Kaur
- Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, Rochester General Hospital, 1425 Portland Avenue, Rochester, NY, 14621, USA.
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Stark JC, Jaroentomeechai T, Moeller TD, Hershewe JM, Warfel KF, Moricz BS, Martini AM, Dubner RS, Hsu KJ, Stevenson TC, Jones BD, DeLisa MP, Jewett MC. On-demand biomanufacturing of protective conjugate vaccines. SCIENCE ADVANCES 2021; 7:eabe9444. [PMID: 33536221 PMCID: PMC7857678 DOI: 10.1126/sciadv.abe9444] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 12/18/2020] [Indexed: 05/19/2023]
Abstract
Conjugate vaccines are among the most effective methods for preventing bacterial infections. However, existing manufacturing approaches limit access to conjugate vaccines due to centralized production and cold chain distribution requirements. To address these limitations, we developed a modular technology for in vitro conjugate vaccine expression (iVAX) in portable, freeze-dried lysates from detoxified, nonpathogenic Escherichia coli. Upon rehydration, iVAX reactions synthesize clinically relevant doses of conjugate vaccines against diverse bacterial pathogens in 1 hour. We show that iVAX-synthesized vaccines against Francisella tularensis subsp. tularensis (type A) strain Schu S4 protected mice from lethal intranasal F. tularensis challenge. The iVAX platform promises to accelerate development of new conjugate vaccines with increased access through refrigeration-independent distribution and portable production.
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Affiliation(s)
- Jessica C Stark
- Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA
- Center for Synthetic Biology, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA
- Chemistry of Life Processes Institute, Northwestern University, 2170 Campus Drive, Evanston, IL 60208-3120, USA
| | - Thapakorn Jaroentomeechai
- Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, 120 Olin Hall, Ithaca, NY 14853, USA
| | - Tyler D Moeller
- Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, 120 Olin Hall, Ithaca, NY 14853, USA
| | - Jasmine M Hershewe
- Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA
- Center for Synthetic Biology, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA
- Chemistry of Life Processes Institute, Northwestern University, 2170 Campus Drive, Evanston, IL 60208-3120, USA
| | - Katherine F Warfel
- Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA
- Center for Synthetic Biology, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA
- Chemistry of Life Processes Institute, Northwestern University, 2170 Campus Drive, Evanston, IL 60208-3120, USA
| | - Bridget S Moricz
- Department of Microbiology and Immunology, University of Iowa, 51 Newton Rd 3-403 Bowen Science Building, Iowa City, IA 52242, USA
| | - Anthony M Martini
- Department of Microbiology and Immunology, University of Iowa, 51 Newton Rd 3-403 Bowen Science Building, Iowa City, IA 52242, USA
| | - Rachel S Dubner
- Department of Biological Sciences, Northwestern University, 2205 Tech Drive Hogan Hall 2144, Evanston, IL 60208-3500, USA
| | - Karen J Hsu
- Department of Mechanical Engineering, Northwestern University, 2145 Sheridan Rd Technological Institute B224, Evanston, IL 60208-3120, USA
| | - Taylor C Stevenson
- Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Weill Hall, Ithaca, NY 14853, USA
| | - Bradley D Jones
- Department of Microbiology and Immunology, University of Iowa, 51 Newton Rd 3-403 Bowen Science Building, Iowa City, IA 52242, USA
- Graduate Program in Genetics, 431 Newton Rd, University of Iowa, Iowa City, IA 52242, USA
| | - Matthew P DeLisa
- Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, 120 Olin Hall, Ithaca, NY 14853, USA.
- Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Weill Hall, Ithaca, NY 14853, USA
| | - Michael C Jewett
- Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA.
- Center for Synthetic Biology, Northwestern University, 2145 Sheridan Rd Technological Institute E136, Evanston, IL 60208-3120, USA
- Chemistry of Life Processes Institute, Northwestern University, 2170 Campus Drive, Evanston, IL 60208-3120, USA
- Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 676 N. St Clair St, Suite 1200, Chicago, IL 60611-3068, USA
- Simpson-Querrey Institute, Northwestern University, 303 E. Superior St, Suite 11-131 Chicago, IL 60611-2875, USA
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27
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Pediatric emergency medicine literature 2020. Am J Emerg Med 2021; 43:123-133. [PMID: 33561621 DOI: 10.1016/j.ajem.2021.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Revised: 01/06/2021] [Accepted: 01/09/2021] [Indexed: 11/22/2022] Open
Abstract
Most children are treated at general Emergency Departments (EDs) and not specialized pediatric EDs. Therefore, it is crucial for emergency medicine physicians to be aware of recent developments in pediatric emergency medicine. Often impactful articles on pediatric emergency medicine are not published in the journals regularly studied by general emergency medicine physicians. We selected ten studies that we found impactful, robust, and relevant for practicing general emergency physicians. This review includes studies of status epilepticus, cardiac arrest, asthma, infant fever, wound care, rapid sequence intubation, coronavirus, and trauma.
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Wangirapan A, Ayuthaya SIN, Katip W, Kasatpibal N, Mektrirat R, Anukool U, Oberdorfer P. Serotypes and Vaccine Coverage of Streptococcus Pneumoniae Colonization in the Nasopharynx of Thai Children in Congested Areas in Chiang Mai. Pathogens 2020; 9:pathogens9120988. [PMID: 33255981 PMCID: PMC7761239 DOI: 10.3390/pathogens9120988] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 11/21/2020] [Accepted: 11/23/2020] [Indexed: 11/16/2022] Open
Abstract
Streptococcus pneumoniae causes around 10% of all deaths in children younger than five years of age. This study aimed to examine the serogroups/serotypes of S. pneumoniae colonization and vaccine serotype coverage of this organism among Thai children. Nasopharyngeal swabs of children less than or equal to 15 years of age were obtained in congested areas in Chiang Mai from 1 February 2013 to 1 August 2013. The serotyping of S. pneumoniae isolates was performed using the ImmuLex™ kit and the vaccine serotype coverage for this organism was evaluated. A total of 292 children were enrolled. One hundred and thirty children (44.5%) had nasopharyngeal colonization with Streptococcus pneumoniae. Eighty-seven (66.9%) isolates were from children younger than five years of age, seventeen (13.1%) were from children aged 6-10 years, and twenty-six (20%) were from children aged 11-15 years. The five most common serogroups/serotypes isolated were 6 (6A, 6B, 6C) (46.1%), 23 (23F, 23A, 23B) (14.6%), 19 (19F, 19A, 19B, 19C) (8.5%), 15 (15F, 15A, 15B, 15C) (6.9%), and 14 (6.1%). Vaccine serotype coverages in pneumococcal conjugate vaccines (PCV):PCV7, PCV10, and PCV13 were 79.1%, 83.6%, and 85.9%, respectively. There were significant increases in coverage between PCV7 and PCV10 (from 79.1% to 83.6%, p < 0.001), PCV7 and PCV13 (from 79.1% to 85.9%, p < 0.001), and PCV10 and PCV13 (from 83.6% to 85.9%, p < 0.001). The majority of pneumococcal serogroup/serotype colonization in the nasopharynx of Thai children in the studied areas was included in the current licensed pneumococcal conjugated vaccines (PCVs). PCV vaccination should be considered for high-risk children to reduce the incidence of invasive pneumococcal disease among Thai children.
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Affiliation(s)
- Anchalee Wangirapan
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (A.W.); (S.I.n.A.)
| | - Satja Issaranggoon na Ayuthaya
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (A.W.); (S.I.n.A.)
| | - Wasan Katip
- Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
- Epidemiology Research Group of Infectious Disease (ERGID), Chiang Mai University, Chiang Mai 50200, Thailand; (N.K.); (R.M.); (U.A.)
- Correspondence: (W.K.); (P.O.); Tel.: +66-5394-4395 (W.K.)
| | - Nongyao Kasatpibal
- Epidemiology Research Group of Infectious Disease (ERGID), Chiang Mai University, Chiang Mai 50200, Thailand; (N.K.); (R.M.); (U.A.)
- Division of Nursing Science, Faculty of Nursing, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Raktham Mektrirat
- Epidemiology Research Group of Infectious Disease (ERGID), Chiang Mai University, Chiang Mai 50200, Thailand; (N.K.); (R.M.); (U.A.)
- Department of Veterinary Bioscience and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Usanee Anukool
- Epidemiology Research Group of Infectious Disease (ERGID), Chiang Mai University, Chiang Mai 50200, Thailand; (N.K.); (R.M.); (U.A.)
- Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Peninnah Oberdorfer
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (A.W.); (S.I.n.A.)
- Epidemiology Research Group of Infectious Disease (ERGID), Chiang Mai University, Chiang Mai 50200, Thailand; (N.K.); (R.M.); (U.A.)
- Correspondence: (W.K.); (P.O.); Tel.: +66-5394-4395 (W.K.)
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Raman R, Brennan J, Ndi D, Sloan C, Markus TM, Schaffner W, Talbot HK. Marked Reduction of Socioeconomic and Racial Disparities in Invasive Pneumococcal Disease Associated With Conjugate Pneumococcal Vaccines. J Infect Dis 2020; 223:1250-1259. [PMID: 32780860 DOI: 10.1093/infdis/jiaa515] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 08/07/2020] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND It is not known whether reductions in socioeconomic and racial disparities in incidence of invasive pneumococcal disease (defined as the isolation of Streptococcus pneumoniae from a normally sterile body site) noted after pneumococcal conjugate vaccine (PCV) introduction have been sustained. METHODS Individual-level data collected from 20 Tennessee counties participating in Active Bacterial Core surveillance over 19 years were linked to neighborhood-level socioeconomic factors. Incidence rates were analyzed across 3 periods-pre-7-valent PCV (pre-PCV7; 1998-1999), pre-13-valent PCV (pre-PCV13; 2001-2009), and post-PCV13 (2011-2016)-by socioeconomic factors. RESULTS A total of 8491 cases of invasive pneumococcal disease were identified. Incidence for invasive pneumococcal disease decreased from 22.9 (1998-1999) to 17.9 (2001-2009) to 12.7 (2011-2016) cases per 100 000 person-years. Post-PCV13 incidence (95% confidence interval [CI]) of PCV13-serotype disease in high- and low-poverty neighborhoods was 3.1 (2.7-3.5) and 1.4 (1.0-1.8), respectively, compared with pre-PCV7 incidence of 17.8 (15.7-19.9) and 6.4 (4.9-7.9). Before PCV introduction, incidence (95% CI) of PCV13-serotype disease was higher in blacks than whites (17.3 [15.1-19.5] vs 11.8 [10.6-13.0], respectively); after introduction, PCV13-type disease incidence was greatly reduced in both groups (white: 2.7 [2.4-3.0]; black: 2.2 [1.8-2.6]). CONCLUSIONS Introduction of PCV13 was associated with substantial reductions in overall incidence and socioeconomic and racial disparities in PCV13-serotype incidence.
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Affiliation(s)
- Rameela Raman
- Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Julia Brennan
- Epidemic Intelligence Service, Division of Scientific Education and Professional Development, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.,Tennessee Department of Health, Nashville, Tennessee, USA
| | - Danielle Ndi
- Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | | | | | | | - H Keipp Talbot
- Vanderbilt University Medical Center, Nashville, Tennessee, USA
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Parameswarappa SG, Pereira CL, Seeberger PH. Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens. Beilstein J Org Chem 2020; 16:1693-1699. [PMID: 32733612 PMCID: PMC7372248 DOI: 10.3762/bjoc.16.140] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 06/18/2020] [Indexed: 01/17/2023] Open
Abstract
Streptococcus pneumoniae (SP) bacteria cause serious invasive diseases. SP bacteria are covered by a capsular polysaccharide (CPS) that is a virulence factor and the basis for SP polysaccharide and glycoconjugate vaccines. The serotype 9V is part of the currently marketed conjugate vaccine and contains an acetate modification. To better understand the importance of glycan modifications in general and acetylation in particular, defined oligosaccharide antigens are needed for serological and immunological studies. Here, we demonstrate a convergent [2 + 3] synthetic strategy to prepare the pentasaccharide repeating unit of 9V with and without an acetate group at the C-6 position of mannosamine.
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Affiliation(s)
- Sharavathi G Parameswarappa
- Max Planck Institute of Colloids and Interfaces, Biomolecular Systems Department, Am Mühlenberg 1, 14476 Potsdam, Germany.,Vaxxilon Deutschland GmbH, Magnusstraße 11, 12489 Berlin, Germany
| | - Claney L Pereira
- Max Planck Institute of Colloids and Interfaces, Biomolecular Systems Department, Am Mühlenberg 1, 14476 Potsdam, Germany.,Vaxxilon Deutschland GmbH, Magnusstraße 11, 12489 Berlin, Germany
| | - Peter H Seeberger
- Max Planck Institute of Colloids and Interfaces, Biomolecular Systems Department, Am Mühlenberg 1, 14476 Potsdam, Germany.,Freie Universität Berlin, Institute for Chemistry and Biochemistry, Arnimallee 22, 14195 Berlin, Germany
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31
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Berry I, Tuite AR, Salomon A, Drews S, Harris AD, Hatchette T, Johnson C, Kwong J, Lojo J, McGeer A, Mermel L, Ng V, Fisman DN. Association of Influenza Activity and Environmental Conditions With the Risk of Invasive Pneumococcal Disease. JAMA Netw Open 2020; 3:e2010167. [PMID: 32658286 PMCID: PMC7358913 DOI: 10.1001/jamanetworkopen.2020.10167] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
IMPORTANCE Streptococcus pneumoniae is the most commonly identified cause of bacterial pneumonia, and invasive pneumococcal disease (IPD) has a high case fatality rate. The wintertime coseasonality of influenza and IPD in temperate countries has suggested that pathogen-pathogen interaction or environmental conditions may contribute to IPD risk. OBJECTIVES To evaluate the short-term associations of influenza activity and environmental exposures with IPD risk in temperate countries and to examine the generalizability of such associations across multiple jurisdictions. DESIGN, SETTING, AND PARTICIPANTS This case-crossover analysis of 19 566 individuals with IPD from 1998 to 2011 combined individual-level outcomes of IPD and population-level exposures. Participants lived in 12 jurisdictions in Canada (the province of Alberta and cities of Toronto, Vancouver, and Halifax), Australia (Perth, Sydney, Adelaide, Brisbane, and Melbourne), and the United States (Baltimore, Providence, and Philadelphia). Data were analyzed in 2019. EXPOSURES Influenza activity, mean temperature, absolute humidity, and UV radiation at delays of 1 to 3 weeks before case occurrence in each jurisdiction. MAIN OUTCOMES AND MEASURES Matched odds ratios (ORs) for IPD associated with changes in exposure variables, estimated using multivariable conditional logistic regression models. Heterogeneity in effects across jurisdictions were evaluated using random-effects meta-analytic models. RESULTS This study included 19 566 patients: 9629 from Australia (mean [SD] age, 42.8 [30.8] years; 5280 [54.8%] men), 8522 from Canada (only case date reported), and 1415 from the United States (only case date reported). In adjusted models, increased influenza activity was associated with increases in IPD risk 2 weeks later (adjusted OR [aOR] per SD increase, 1.07; 95% CI, 1.01-1.13). Increased humidity was associated with decreased IPD risk 1 week later (aOR per 1 g/m3, 0.98; 95% CI, 0.96-1.00). Other associations were heterogeneous; metaregression suggested that combinations of environmental factors might represent unique local risk signatures. For example, the heterogeneity in effects of UV radiation and humidity at a 2-week lag was partially explained by variation in temperature (UV index: coefficient, 0.0261; 95% CI, 0.0078 to 0.0444; absolute humidity: coefficient, -0.0077; 95% CI, -0.0125 to -0.0030). CONCLUSIONS AND RELEVANCE In this study, influenza was associated with increased IPD risk in temperate countries. This association was not explained by coseasonality or case characteristics and appears generalizable. Absolute humidity was associated with decreased IPD risk in the same jurisdictions. The generalizable nature of these associations has important implications for influenza control and advances the understanding of the seasonality of this important disease.
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Affiliation(s)
- Isha Berry
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Ashleigh R. Tuite
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Angela Salomon
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Steven Drews
- Canadian Blood Services, Ottawa, Ontario, Canada
- University of Alberta, Edmonton, Alberta, Canada
| | | | - Todd Hatchette
- Nova Scotia Health Authority, Halifax, Nova Scotia, Canada
- Dalhousie University, Halifax, Nova Scotia, Canada
| | - Caroline Johnson
- Philadelphia Department of Public Health, Philadelphia, Pennsylvania
| | - Jeff Kwong
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Jose Lojo
- Philadelphia Department of Public Health, Philadelphia, Pennsylvania
| | - Allison McGeer
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Leonard Mermel
- Warren Alpert School of Medicine of Brown University, Providence, Rhode Island
- Rhode Island Hospital, Providence
| | - Victoria Ng
- Public Health Agency of Canada, Guelph, Ontario, Canada
| | - David N. Fisman
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
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32
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Baxter R, Aukes L, Pelton SI, Yee A, Klein NP, Gruber WC, Scott DA, Center KJ. Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease After Introduction Into Routine Pediatric Use. J Pediatric Infect Dis Soc 2020; 10:141-150. [PMID: 32415771 PMCID: PMC7996647 DOI: 10.1093/jpids/piaa035] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Accepted: 04/08/2020] [Indexed: 11/14/2022]
Abstract
BACKGROUND In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced 7-valent PCV (PCV7) for protection against invasive pneumococcal disease (IPD). This study used laboratory surveillance data to examine the effect of PCV13 on IPD before and after PCV13 introduction among children aged 6 weeks to <6 years and those aged ≥6 weeks. METHODS Observational laboratory-based IPD surveillance data were compared for the periods May 2010-April 2018 and May 2008-April 2010 (the PCV7 period) using a database of Kaiser Permanente Northern California (KPNC) members with laboratory-confirmed IPD. RESULTS Among children aged 6 weeks to 6 years, overall IPD incidence decreased from 11.57 per 100 000 during the PCV7 period to 4.09 per 100 000 after PCV13 introduction; PCV13-type IPD incidence decreased from 5.12 to 0.84 per 100 000. Non-PCV13-serotype IPD did not change significantly in this age group (PCV7 period, 1.71 per 100 000 and after PCV13, 2.52 per 100 000). Of cases occurring in this group, bacteremia was the most common clinical diagnosis. Across all ages, IPD decreased from 9.49 to 6.23 per 100 000 and PCV13-type IPD decreased from 4.67 to 1.89 per 100 000, changes being mostly due to decreases in serotypes 19A and 7F. IPD caused by non-PCV13 serotypes did not change (3.34 and 3.35 per 100 000). Overall, pneumococci isolated after PCV13 introduction had increased susceptibility to penicillin, cefotaxime, and ceftriaxone.This prospective, laboratory-based surveillance study in Kaiser Permanente Northern California members examined annual IPD incidence before and after PCV13 introduction. In children aged 6 weeks to <6 years, IPD caused by PCV13 serotypes decreased significantly (84%) during the surveillance period. CONCLUSIONS IPD incidence decreased further in every age group after PCV13 introduction, suggesting both direct vaccination effects in the infant population and indirect effects in adults. CLINICAL TRIALS REGISTRATION NCT01128439.
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Affiliation(s)
- Roger Baxter
- Vaccine Study Center, Kaiser Permanente, Oakland, California, USA
| | - Laurie Aukes
- Vaccine Study Center, Kaiser Permanente, Oakland, California, USA,Correspondence: Laurie Aukes, Kaiser Permanente Vaccine Study Center, 1 Kaiser Plaza, Ordway Bldg 16th Floor, Oakland, CA 94612 USA ()
| | - Stephen I Pelton
- Department of Pediatrics, Boston University School of Public Health, Boston, Massachusetts, USA,Department of Pediatrics, Boston Medical Center, Boston, Massachusetts, USA
| | - Arnold Yee
- Vaccine Study Center, Kaiser Permanente, Oakland, California, USA
| | - Nicola P Klein
- Vaccine Study Center, Kaiser Permanente, Oakland, California, USA
| | - William C Gruber
- Vaccine Clinical Research and Development, Pfizer Inc, Pearl River, New York, USA
| | - Daniel A Scott
- VaccineClinical Research and Development, Pfizer Inc, Collegeville, Pennsylvania, USA
| | - Kimberly J Center
- VaccineClinical Research and Development, Pfizer Inc, Collegeville, Pennsylvania, USA
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Lyons TW, Garro AC, Cruz AT, Freedman SB, Okada PJ, Mahajan P, Balamuth F, Thompson AD, Kulik DM, Uspal NG, Arms JL, Nigrovic LE. Performance of the Modified Boston and Philadelphia Criteria for Invasive Bacterial Infections. Pediatrics 2020; 145:peds.2019-3538. [PMID: 32205466 DOI: 10.1542/peds.2019-3538] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/06/2020] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND The ability of the decades-old Boston and Philadelphia criteria to accurately identify infants at low risk for serious bacterial infections has not been recently reevaluated. METHODS We assembled a multicenter cohort of infants 29 to 60 days of age who had cerebrospinal fluid (CSF) and blood cultures obtained. We report the performance of the modified Boston criteria (peripheral white blood cell count [WBC] ≥20 000 cells per mm3, CSF WBC ≥10 cells per mm3, and urinalysis with >10 WBC per high-power field or positive urine dip result) and modified Philadelphia criteria (peripheral WBC ≥15 000 cells per mm3, CSF WBC ≥8 cells per mm3, positive CSF Gram-stain result, and urinalysis with >10 WBC per high-power field or positive urine dip result) for the identification of invasive bacterial infections (IBIs). We defined IBI as bacterial meningitis (growth of pathogenic bacteria from CSF culture) or bacteremia (growth from blood culture). RESULTS We applied the modified Boston criteria to 8344 infants and the modified Philadelphia criteria to 8131 infants. The modified Boston criteria identified 133 of the 212 infants with IBI (sensitivity 62.7% [95% confidence interval (CI) 55.9% to 69.3%] and specificity 59.2% [95% CI 58.1% to 60.2%]), and the modified Philadelphia criteria identified 157 of the 219 infants with IBI (sensitivity 71.7% [95% CI 65.2% to 77.6%] and specificity 46.1% [95% CI 45.0% to 47.2%]). The modified Boston and Philadelphia criteria misclassified 17 of 53 (32.1%) and 13 of 56 (23.3%) infants with bacterial meningitis, respectively. CONCLUSIONS The modified Boston and Philadelphia criteria misclassified a substantial number of infants 29 to 60 days old with IBI, including those with bacterial meningitis.
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Affiliation(s)
- Todd W Lyons
- Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts;
| | - Aris C Garro
- Departments of Pediatrics and Emergency Medicine, Brown University and Rhode Island Hospital, Providence, Rhode Island
| | - Andrea T Cruz
- Sections of Pediatric Emergency Medicine and Pediatric Infectious Diseases, Baylor College of Medicine, Houston, Texas
| | - Stephen B Freedman
- Sections of Pediatric Emergency Medicine and Gastroenterology, Alberta Children's Hospital and Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Pamela J Okada
- Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Prashant Mahajan
- Departments of Emergency Medicine and Pediatrics, Medical School, University of Michigan, Ann Arbor, Michigan
| | - Fran Balamuth
- Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Amy D Thompson
- Departments of Pediatrics and Emergency Medicine, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware
| | - Dina M Kulik
- Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Neil G Uspal
- Department of Pediatrics, University of Washington, Seattle Children's Hospital, Seattle, Washington; and
| | - Joseph L Arms
- Department of Pediatrics, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota
| | - Lise E Nigrovic
- Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts
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Yildirim I, Pelton SI. Infants at Risk for Invasive Pneumococcal Disease in the 13-Valent Pneumococcal Conjugate Vaccine Era. Clin Infect Dis 2020; 69:91-92. [PMID: 30281070 DOI: 10.1093/cid/ciy848] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Accepted: 10/01/2018] [Indexed: 11/13/2022] Open
Affiliation(s)
- Inci Yildirim
- Division of Pediatric Infectious Diseases, Emory University School of Medicine.,Department of Epidemiology, Rollins School of Public Health, Atlanta, Georgia
| | - Stephen I Pelton
- Schools of Medicine and Public Health, Boston University.,Division of Pediatric Infectious Diseases, Boston Medical Center, Massachusetts
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35
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Decline in childhood respiratory-related mortality after the introduction of the pneumococcal conjugate vaccine in Morocco. J Infect Public Health 2020; 13:402-406. [DOI: 10.1016/j.jiph.2019.06.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2018] [Revised: 06/19/2019] [Accepted: 06/20/2019] [Indexed: 11/22/2022] Open
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Nguyen DK, Friedlander S, Fleischman RJ, Zangwill KM. Length of Stay and Complications Associated With Febrile Infants <90 Days of Age Hospitalized in the United States, 2000-2012. Hosp Pediatr 2019; 8:746-752. [PMID: 30482790 DOI: 10.1542/hpeds.2018-0132] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OBJECTIVES It is not known how changes in the epidemiology of serious bacterial infection (SBI) and greater availability of rapid viral diagnostic tests have impacted the hospital length of stay (LOS) and associated complications among young infants with suspected SBI. METHODS We used national administrative data from the Healthcare Cost and Utilization Project Kids' Inpatient Database and other state-specific data to identify febrile infants <90 days of age hospitalized in 2000, 2003, 2006, 2009, and 2012. We used multivariate analysis to determine LOS, risk factors for prolonged LOS, and complications of care among infants with isolated fever or viral respiratory disease, without concomitant serious infection. RESULTS We identified 44 875 infants. LOS for each clinical group did not change over time in a clinically significant way. Mean LOS was ≤2 days for approximately two-thirds of all infants and ≥4 days for 11% in each clinical group. Factors associated with longer LOS included age <31 days, critical clinical status, concomitant chronic disease, and the presence of complications (P < .05). We identified 289 (0.8%) infants with 351 complications of care, 18 (6%) of whom had >1. These infants had longer LOS (P < .001), and those with chronic disease and older age were at increased risk (P < .01). CONCLUSIONS Despite the changing epidemiology of SBI and increased availability of viral diagnostic testing, we did not detect a clinically significant change in LOS for febrile infants with suspected SBI. Complications associated with hospitalization of these infants was associated with increased LOS.
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Affiliation(s)
- Diana K Nguyen
- Division of Pediatric Infectious Diseases, Departments of Pediatrics and
| | - Scott Friedlander
- Los Angeles Biomedical Research Institute, Harbor-University of California, Los Angeles Medical Center, Torrance, California
| | - Ross J Fleischman
- Los Angeles Biomedical Research Institute, Harbor-University of California, Los Angeles Medical Center, Torrance, California.,Emergency Medicine, and
| | - Kenneth M Zangwill
- Division of Pediatric Infectious Diseases, Departments of Pediatrics and .,Los Angeles Biomedical Research Institute, Harbor-University of California, Los Angeles Medical Center, Torrance, California
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37
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Anderson EJ, Daugherty MA, Pickering LK, Orenstein WA, Yogev R. Protecting the Community Through Child Vaccination. Clin Infect Dis 2019; 67:464-471. [PMID: 29471452 DOI: 10.1093/cid/ciy142] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Accepted: 02/15/2018] [Indexed: 11/14/2022] Open
Abstract
The direct impact of vaccines on children is well described, but the major public health impact of indirect protection provided to the community by vaccines is underappreciated. Community protection occurs when vaccinated persons block the chain of transmission, protecting undervaccinated or unvaccinated susceptible community members by preventing exposure and limiting the spread of the pathogen through the community. Substantial declines in disease incidence have occurred shortly after implementing new childhood vaccines, including declines among vaccine-ineligible children, adolescents, and adults. Protection of susceptible community members depends on maintaining high vaccination rates. Improved recognition of community protection will strengthen childhood vaccination strategies that will protect our communities into the future.
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Affiliation(s)
- Evan J Anderson
- Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.,Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Michael A Daugherty
- Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.,Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Larry K Pickering
- Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
| | - Walter A Orenstein
- Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.,Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Ram Yogev
- Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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38
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McLaughlin JM, Jiang Q, Gessner BD, Swerdlow DL, Sings HL, Isturiz RE, Jodar L. Pneumococcal conjugate vaccine against serotype 3 pneumococcal pneumonia in adults: A systematic review and pooled analysis. Vaccine 2019; 37:6310-6316. [DOI: 10.1016/j.vaccine.2019.08.059] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 05/17/2019] [Accepted: 08/22/2019] [Indexed: 11/26/2022]
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39
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Rathore MH. The Febrile Infant: Where Art Meets Science to Prevent Harm. Pediatr Rev 2019; 40:6-7. [PMID: 31575683 DOI: 10.1542/pir.2019-40s06] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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40
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Vardanjani HM, Borna H, Ahmadi A. Effectiveness of pneumococcal conjugate vaccination against invasive pneumococcal disease among children with and those without HIV infection: a systematic review and meta-analysis. BMC Infect Dis 2019; 19:685. [PMID: 31382917 PMCID: PMC6683423 DOI: 10.1186/s12879-019-4325-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Accepted: 07/26/2019] [Indexed: 01/11/2023] Open
Abstract
Background HIV-infected children are at a higher risk of Invasive Pneumococcal Disease (IPD) and its mortality, even in the era of antiretroviral therapy. Therefore, an effective vaccination strategy would be beneficial. To investigate the effectiveness of Pneumococcal Conjugate Vaccination (PCV) against IPD among HIV-Infected and HIV-Uninfected Children through a systematic review and meta-analysis. Methods Observational studies and randomized trials on 7 years old or older children were searched in the Cochrane Library, Web of Science core collection, Embase, Medline/PubMed, and Google Scholar. Critical appraisal was done using the Cochrane risk of bias tool and the Newcastle-Ottawa quality assessment form. Effectiveness and efficacy of at least one dose of PCV was investigated among children with and without HIV considering subgroups of pneumococcal serotypes. We meta-analyzed the effect sizes using random-effects modeling. Results Efficacy of PCV was estimated as 45.0% (31.2, 56.1) and 52.6% (25.7, 69.8) among HIV-infected and HIV-uninfected children, respectively. Effectiveness of PCV among HIV-infected children as − 6.2% (− 67.6, 32.7) was significantly lower than HIV-uninfected children 65.1% (47.3, 76.9). Effectiveness of PCV among HIV-infected children for IPDs caused by vaccine serotypes was estimated as 7.7(− 66.7, 48.9), and for IPDs caused by non-vaccine serotypes was estimated as − 402.8(− 1856, − 29.2). Conclusion Unlike the evidence on the efficacy of PCV against IPD among both of HIV-infected and HIV-uninfected children, its effectiveness against IPD among HIV-infected children is much less limited. Review registration The study protocol was registered at PROSPERO (registration ID: CRD42018108187). Electronic supplementary material The online version of this article (10.1186/s12879-019-4325-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Hossein Molavi Vardanjani
- Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Hodjat Borna
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Ali Ahmadi
- Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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Moodley K, Coovadia YM, Cohen C, Meiring S, Lengana S, De Gouveia L, von Mollendorf C, Crowther-Gibson P, Quan V, Eley B, Reubenson G, Nana T, von Gottberg A. Invasive Pneumococcal Disease in Neonates Prior to Pneumococcal Conjugate Vaccine Use in South Africa: 2003-2008. Pediatr Infect Dis J 2019; 38:424-430. [PMID: 30882740 DOI: 10.1097/inf.0000000000002096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Neonatal invasive pneumococcal disease (IPD) in developing countries is poorly described. We provide a baseline description of neonatal IPD in South Africa, before implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2009. METHODS Data from children (age ≤ 2 years) with IPD (pneumococcus identified from a normally sterile specimen) from January 2003 to December 2008 were extracted from a national laboratory-based surveillance database. Clinical and laboratory characteristics of IPD among neonates (0-27 days old) was compared with IPD among young children (≥ 28 days ≤ 2 years). Early-onset IPD (0-6 days old) was compared with late-onset IPD (≥ 7-27 days old). Isolates were serotyped using the Quellung reaction. RESULTS Overall 27,630 IPD cases were reported. Of the 26,277 (95%) with known ages, 6583 (25%) were ≤ 2 years of age, of which 4.5% (294/6583) were neonates. The estimated annual incidence of neonatal IPD in 2008 was 5 per 100,000 live births. Fifty-one percent of neonates with IPD presented with early-onset IPD. Case fatality ratios (CFRs) were high in both groups, 31% (28/89) in neonatal IPD versus 26% (614/2383) in non-neonatal IPD (P = 0.18). Among neonates, the meningitis cases (15/37, 41%) were associated with the highest CFR. The 13-valent pneumococcal conjugate vaccine (PCV13) serotypes accounted for 69% (134/194) of neonatal IPD isolates. CONCLUSIONS Pneumococcal neonatal disease in South Africa was not uncommon before PCV introduction and is associated with a high CFR. The indirect effect on neonatal IPD of PCV rollout requires further evaluation.
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Affiliation(s)
- Krishnee Moodley
- From the Microbiology, Lancet Laboratories, Kwa-Zulu Natal
- Antimicrobial Research Unit, College of Health Sciences, University of Kwa-Zulu-Natal, Durban
| | - Yacoob Mahomed Coovadia
- Department of Medical Microbiology, Nelson R Mandela School of Medicine, University of Kwa-Zulu Natal, Durban
| | - Cheryl Cohen
- School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg
- Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg
| | - Susan Meiring
- Division of Public Health Surveillance and Response, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg
| | - Sarona Lengana
- Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg
| | - Linda De Gouveia
- Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg
| | - Claire von Mollendorf
- School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg
- Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg
| | - Penny Crowther-Gibson
- Division of Public Health Surveillance and Response, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg
| | - Vanessa Quan
- Division of Public Health Surveillance and Response, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg
| | - Brian Eley
- Pediatric Infectious Diseases Unit, Red Cross War Memorial Children's Hospital, Department of Pediatrics and Child Health, University of Cape Town, Cape Town
| | - Gary Reubenson
- Rahima Moosa Mother and Child Hospital, Department of Pediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng
| | - Trusha Nana
- Department of Microbiology, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Services, Johannesburg
| | - Anne von Gottberg
- Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg
- School of Pathology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
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Aydogan S, Dilli D, Ozyazıcı A, Cakmakci E, Koyuncu E, Zenciroğlu A. Central Diabetes Insipidus in an Infant with Pneumococcal Meningitis. Fetal Pediatr Pathol 2019; 38:80-84. [PMID: 30580673 DOI: 10.1080/15513815.2018.1547335] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
BACKGROUND Central diabetes is an infrequent complication reported in the neonatal period. CASE REPORT CDI as a complication of Streptococcus pneumoniae (S. pneumoniae) sepsis and meningitis in a 9-day-old boy is presented. The CDI developed on day 3 after admission and was controlled with nasal vasopressin on the 20th day of admission. Despite antibiotic support, the child died from Acinetobacter sepsis at 4 months of age, but the CDI was well controlled. CONCLUSION Newborns with bacterial meningitis can develop CDI as a sequalae. Treatment of the CDI with nasal vasopressin can be successful in this period. To our knowledge, this is the first newborn of CDI associated with S. pneumoniae meningitis.
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Affiliation(s)
- Seda Aydogan
- a Neonatology , University of Health Sciences, Dr Sami Ulus Maternity and Children Health and Research Application Center , Ankara , Türkiye
| | - Dilek Dilli
- a Neonatology , University of Health Sciences, Dr Sami Ulus Maternity and Children Health and Research Application Center , Ankara , Türkiye
| | - Ahmet Ozyazıcı
- a Neonatology , University of Health Sciences, Dr Sami Ulus Maternity and Children Health and Research Application Center , Ankara , Türkiye
| | - Emin Cakmakci
- b Radiology, University of Health Sciences, Dr Sami Ulus Maternity and Children Health and Research Application Center , Ankara , Türkiye
| | - Ece Koyuncu
- a Neonatology , University of Health Sciences, Dr Sami Ulus Maternity and Children Health and Research Application Center , Ankara , Türkiye
| | - Ayşegül Zenciroğlu
- a Neonatology , University of Health Sciences, Dr Sami Ulus Maternity and Children Health and Research Application Center , Ankara , Türkiye
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Govindan A, Zhu Y, Azmy MC, Lee YJ, Kalyoussef E. Pediatric Human Immunodeficiency Virus and Otolaryngologic Manifestations: An Analysis of Hospital Admissions From 1997 to 2012. Laryngoscope 2019; 129:E377-E382. [PMID: 30667060 DOI: 10.1002/lary.27778] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 11/04/2018] [Accepted: 12/10/2018] [Indexed: 11/06/2022]
Abstract
OBJECTIVES/HYPOTHESIS Many human immunodeficiency virus (HIV)-infected pediatric patients develop otolaryngologic disease. We aimed to characterize their otolaryngologic manifestations by type and demographic variation, and model temporal trends. STUDY DESIGN Retrospective cohort review. METHODS A retrospective review utilizing the Kids' Inpatient Database (KID) was conducted. International Classification of Diseases, Ninth Revision, Clinical Modification codes for HIV and otolaryngologic diagnoses were used to query data from the triennially published KID files from 1997 to 2012. A subset analysis of infectious versus non-infectious admitting otolaryngologic diagnoses was conducted. RESULTS A total of 11,150 cases met the inclusion criteria. Of these cases, 21.8% were admitted for otolaryngologic manifestations, with 18.0% presenting with infectious symptomatology, 4.8% with noninfectious disease, and 1.0% with both. On average, patients presenting with infectious disease were younger (8.17 years vs. 9.65 years, P < .001). Patients in the South were significantly more likely to be admitted for infection (54.8% vs. 42.0%, P < .001), with non-infectious predominance in the Northeast and West. HIV-infected children in 1997 were more likely to present with infectious otolaryngologic disease (56.3% vs. 45.8%, P < .001); however, there has been a decrease in the prevalence of infectious head and neck presentations (46.5%, 19.9%, 11.5%, 6.7%, 3.7%, and 1.9% from 1997 to 2012), and a gradual shift toward noninfectious manifestation with notable differences in 2000 and 2012 (19.9% vs. 25.2%; P = .017; and 1.9% vs. 4.8%, P < .001, respectively). CONCLUSIONS Otolaryngologic disease accounts for nearly one-fifth of hospitalizations in HIV-infected children; however, rates of hospitalization as well as otolaryngologic manifestations have progressively decreased over time. HIV-infected children nowadays are more likely to present with noninfectious rather than infectious disease. LEVEL OF EVIDENCE NA Laryngoscope, 129:E377-E382, 2019.
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Affiliation(s)
- Aparna Govindan
- Department of Otolaryngology-Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, U.S.A
| | - Yan Zhu
- Department of Otolaryngology-Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, U.S.A
| | - Monica C Azmy
- Department of Otolaryngology-Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, U.S.A
| | - Yung-Jae Lee
- Department of Otolaryngology-Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, U.S.A
| | - Evelyne Kalyoussef
- Department of Otolaryngology-Head and Neck Surgery, Rutgers New Jersey Medical School, Newark, New Jersey, U.S.A
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Aronson PL, McCulloh RJ, Tieder JS, Nigrovic LE, Leazer RC, Alpern ER, Feldman EA, Balamuth F, Browning WL, Neuman MI. Application of the Rochester Criteria to Identify Febrile Infants With Bacteremia and Meningitis. Pediatr Emerg Care 2019; 35:22-27. [PMID: 29406479 PMCID: PMC6915062 DOI: 10.1097/pec.0000000000001421] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES The Rochester criteria were developed to identify febrile infants aged 60 days or younger at low-risk of bacterial infection and do not include cerebrospinal fluid (CSF) testing. Prior studies have not specifically assessed criteria performance for bacteremia and bacterial meningitis (invasive bacterial infection). Our objective was to determine the sensitivity of the Rochester criteria for detection of invasive bacterial infection. METHODS Retrospective cohort study of febrile infants aged 60 days or younger with invasive bacterial infections evaluated at 8 pediatric emergency departments from July 1, 2012, to June 30, 2014. Potential cases were identified from the Pediatric Health Information System using International Classification of Diseases, Ninth Revision diagnosis codes for bacteremia, meningitis, urinary tract infection, and fever. Medical record review was then performed to confirm presence of an invasive bacterial infection and to evaluate the Rochester criteria: medical history, symptoms or ill appearance, results of urinalysis, complete blood count, CSF testing (if obtained), and blood, urine, and CSF culture. An invasive bacterial infection was defined as growth of pathogenic bacteria from blood or CSF culture. RESULTS Among 82 febrile infants aged 60 days or younger with invasive bacterial infection, the sensitivity of the Rochester criteria were 92.7% (95% confidence interval [CI], 84.9%-96.6%) overall, 91.7% (95% CI, 80.5%-96.7%) for neonates 28 days or younger, and 94.1% (95% CI, 80.9%-98.4%) for infants aged 29 to 60 days old. Six infants with bacteremia, including 1 neonate with bacterial meningitis, met low-risk criteria. CONCLUSIONS The Rochester criteria identified 92% of infants aged 60 days or younger with invasive bacterial infection. However, 1 neonate 28 days or younger with meningitis was classified as low-risk.
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Affiliation(s)
- Paul L. Aronson
- Departments of Pediatrics and Emergency Medicine, Section of Pediatric Emergency Medicine, Yale School of Medicine, New Haven, CT,§ Address Correspondence to: Paul L. Aronson, MD, Section of Pediatric Emergency Medicine, Yale School of Medicine, 100 York Street, Suite 1F, New Haven, CT, 06511. Phone: 203-737-7443, Fax: 203-737-7447,
| | - Russell J. McCulloh
- Division of Infectious Diseases, Department of Pediatrics, Children’s Mercy Hospital, University of Missouri–Kansas City School of Medicine, Kansas City, MO
| | - Joel S. Tieder
- Division of Hospital Medicine, Department of Pediatrics, Seattle Children’s Hospital, Seattle, WA,University of Washington School of Medicine, Seattle, WA
| | - Lise E. Nigrovic
- Division of Emergency Medicine, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Rianna C. Leazer
- Division of Hospital Medicine, Department of Pediatrics, Children’s Hospital of the King’s Daughters, Norfolk, VA
| | - Elizabeth R. Alpern
- Division of Emergency Medicine, Ann and Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
| | | | - Fran Balamuth
- The Center for Pediatric Clinical Effectiveness and Division of Emergency Medicine, Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
| | - Whitney L. Browning
- Division of Hospital Medicine, Department of Pediatrics, The Monroe Carell Jr Children’s Hospital at Vanderbilt, Vanderbilt University School of Medicine, Nashville, TN
| | - Mark I. Neuman
- Division of Emergency Medicine, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA
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Dunne EM, Satzke C, Ratu FT, Neal EFG, Boelsen LK, Matanitobua S, Pell CL, Nation ML, Ortika BD, Reyburn R, Jenkins K, Nguyen C, Gould K, Hinds J, Tikoduadua L, Kado J, Rafai E, Kama M, Mulholland EK, Russell FM. Effect of ten-valent pneumococcal conjugate vaccine introduction on pneumococcal carriage in Fiji: results from four annual cross-sectional carriage surveys. Lancet Glob Health 2018; 6:e1375-e1385. [PMID: 30420033 PMCID: PMC6231327 DOI: 10.1016/s2214-109x(18)30383-8] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 07/12/2018] [Accepted: 08/07/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND The indirect effects of pneumococcal conjugate vaccines (PCVs) are mediated through reductions in carriage of vaccine serotypes. Data on PCVs in Asia and the Pacific are scarce. Fiji introduced the ten-valent PCV (PCV10) in 2012, with a schedule consisting of three priming doses at 6, 10, and 14 weeks of age and no booster dose (3 + 0 schedule) without catch-up. We investigated the effects of PCV10 introduction using cross-sectional nasopharyngeal carriage surveys. METHODS We did four annual carriage surveys (one pre-PCV10 and three post-PCV10) in the greater Suva area in Fiji, during 2012-15, of 5-8-week-old infants, 12-23-month-old children, 2-6-year-old children, and their caregivers (total of 8109 participants). Eligible participants were of appropriate age, had axillary temperature lower than 37°C, and had lived in the community for at least 3 consecutive months. We used purposive quota sampling to ensure a proper representation of the Fiji population. Pneumococci were detected by real-time quantitative PCR, and molecular serotyping was done with microarray. FINDINGS 3 years after PCV10 introduction, vaccine-serotype carriage prevalence declined, with adjusted prevalences (2015 vs 2012) of 0·56 (95% CI 0·34-0·93) in 5-8-week-old infants, 0·34 (0·23-0·49) in 12-23-month-olds, 0·47 (0·34-0·66) in 2-6-year-olds, and 0·43 (0·13-1·42) in caregivers. Reductions in PCV10 serotype carriage were evident in both main ethnic groups in Fiji; however, carriage of non-PCV10 serotypes increased in Indigenous Fijian infants and children. Density of PCV10 serotypes and non-PCV10 serotypes was lower in PCV10-vaccinated children aged 12-23 months than in PCV10-unvaccinated children of the same age group (PCV10 serotypes -0·56 [95% CI -0·98 to -0·15], p=0·0077; non-PCV10 serotypes -0·29 [-0·57 to -0·02], p=0·0334). INTERPRETATION Direct and indirect effects on pneumococcal carriage post-PCV10 are likely to result in reductions in pneumococcal disease, including in infants too young to be vaccinated. Serotype replacement in carriage in Fijian children, particularly Indigenous children, warrants further monitoring. Observed changes in pneumococcal density might be temporal rather than vaccine related. FUNDING Department of Foreign Affairs and Trade of the Australian Government through the Fiji Health Sector Support Program; Victorian Government's Operational Infrastructure Support Program; Bill & Melinda Gates Foundation.
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Affiliation(s)
- Eileen M Dunne
- Pneumococcal Research, Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia.
| | - Catherine Satzke
- Pneumococcal Research, Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia; Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, Australia
| | | | - Eleanor F G Neal
- Pneumococcal Research, Murdoch Children's Research Institute, Parkville, VIC, Australia
| | - Laura K Boelsen
- Pneumococcal Research, Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia
| | | | - Casey L Pell
- Pneumococcal Research, Murdoch Children's Research Institute, Parkville, VIC, Australia
| | - Monica L Nation
- Pneumococcal Research, Murdoch Children's Research Institute, Parkville, VIC, Australia
| | - Belinda D Ortika
- Pneumococcal Research, Murdoch Children's Research Institute, Parkville, VIC, Australia
| | - Rita Reyburn
- Pneumococcal Research, Murdoch Children's Research Institute, Parkville, VIC, Australia
| | - Kylie Jenkins
- Fiji Health Sector Support Program, Suva, Fiji; Telethon Kids Institute, Subiaco, WA, Australia
| | - Cattram Nguyen
- Pneumococcal Research, Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia
| | - Katherine Gould
- Institute for Infection and Immunity, St George's, University of London, UK; BUGS Bioscience, London Bioscience Innovation Centre, London, UK
| | - Jason Hinds
- Institute for Infection and Immunity, St George's, University of London, UK; BUGS Bioscience, London Bioscience Innovation Centre, London, UK
| | | | - Joseph Kado
- Ministry of Health and Medical Services, Suva, Fiji; Telethon Kids Institute, Subiaco, WA, Australia; College of Medicine Nursing and Health Sciences, Fiji National University, Suva, Fiji
| | - Eric Rafai
- Ministry of Health and Medical Services, Suva, Fiji
| | - Mike Kama
- Ministry of Health and Medical Services, Suva, Fiji
| | - E Kim Mulholland
- Pneumococcal Research, Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia; London School of Hygiene & Tropical Medicine, London, UK
| | - Fiona M Russell
- Pneumococcal Research, Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia
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Satzke C, Dunne EM, Choummanivong M, Ortika BD, Neal EFG, Pell CL, Nation ML, Fox KK, Nguyen CD, Gould KA, Hinds J, Chanthongthip A, Xeuatvongsa A, Mulholland EK, Sychareun V, Russell FM. Pneumococcal carriage in vaccine-eligible children and unvaccinated infants in Lao PDR two years following the introduction of the 13-valent pneumococcal conjugate vaccine. Vaccine 2018; 37:296-305. [PMID: 30502068 DOI: 10.1016/j.vaccine.2018.10.077] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 10/11/2018] [Accepted: 10/23/2018] [Indexed: 01/27/2023]
Abstract
Pneumococcal carriage is a prerequisite for disease, and underpins herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few data on the impact of PCVs in lower income settings, particularly in Asia. In 2013, the Lao People's Democratic Republic (Lao PDR) introduced 13-valent PCV (PCV13) as a 3 + 0 schedule (doses at 6, 10 and 14 weeks of age) with limited catch-up vaccination. We conducted two cross-sectional carriage surveys (pre- and two years post-PCV) to assess the impact of PCV13 on nasopharyngeal pneumococcal carriage in 5-8 week old infants (n = 1000) and 12-23 month old children (n = 1010). Pneumococci were detected by quantitative real-time PCR, and molecular serotyping was performed using DNA microarray. Post PCV13, there was a 23% relative reduction in PCV13-type carriage in children aged 12-23 months (adjusted prevalence ratio [aPR] 0.77 [0.61-0.96]), and no significant change in non-PCV13 serotype carriage (aPR 1.11 [0.89-1.38]). In infants too young to be vaccinated, there was no significant change in carriage of PCV13 serotypes (aPR 0.74 [0.43-1.27]) or non-PCV13 serotypes (aPR 1.29 [0.85-1.96]), although trends were suggestive of indirect effects. Over 70% of pneumococcal-positive samples contained at least one antimicrobial resistance gene, which were more common in PCV13 serotypes (p < 0.001). In 12-23 month old children, pneumococcal density of both PCV13 serotypes and non-PCV13 serotypes was higher in PCV13-vaccinated compared with undervaccinated children (p = 0.004 and p < 0.001, respectively). This study provides evidence of PCV13 impact on carriage in a population without prior PCV7 utilisation, and provides important data from a lower-middle income setting in Asia. The reductions in PCV13 serotype carriage in vaccine-eligible children are likely to result in reductions in pneumococcal transmission and disease in Lao PDR.
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Affiliation(s)
- Catherine Satzke
- Pneumococcal Research, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Australia.
| | - Eileen M Dunne
- Pneumococcal Research, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Australia
| | | | - Belinda D Ortika
- Pneumococcal Research, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Australia
| | - Eleanor F G Neal
- Pneumococcal Research, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Australia; Centre for International Child Health, Department of Paediatrics, The University of Melbourne, Parkville, Australia
| | - Casey L Pell
- Pneumococcal Research, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Australia
| | - Monica L Nation
- Pneumococcal Research, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Australia
| | - Kimberley K Fox
- Expanded Programme on Immunization, World Health Organization Regional Office for the Western Pacific, Manila, Philippines
| | - Cattram D Nguyen
- Pneumococcal Research, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Australia
| | - Katherine A Gould
- Institute for Infection and Immunity, St. George's, University of London, London, UK; BUGS Bioscience, London Bioscience Innovation Centre, London, UK
| | - Jason Hinds
- Institute for Infection and Immunity, St. George's, University of London, London, UK; BUGS Bioscience, London Bioscience Innovation Centre, London, UK
| | - Anisone Chanthongthip
- Laos-Oxford-Mahosot Hospital Wellcome Trust Research Unit, Vientiane, Lao People's Democratic Republic
| | | | - E Kim Mulholland
- Pneumococcal Research, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Australia; Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | | | - Fiona M Russell
- Pneumococcal Research, Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Australia; Department of Paediatrics, The University of Melbourne, Parkville, Australia; Centre for International Child Health, Department of Paediatrics, The University of Melbourne, Parkville, Australia
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Outpacing the pneumococcus: Antibody dynamics in the first few days following pneumococcal capsular antigen stimulation. Sci Rep 2018; 8:15376. [PMID: 30337597 PMCID: PMC6193966 DOI: 10.1038/s41598-018-33735-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Accepted: 09/19/2018] [Indexed: 11/08/2022] Open
Abstract
Children in developing countries are frequently exposed to the pneumococcus, but few develop invasive pneumococcal disease (IPD). We test the hypothesis that natural variation exists in the rapidity of IgG responses following exposure to pneumococcal polysaccharides, and that these differences are sufficiently great to affect susceptibility to and outcome of IPD. We recruited children aged 24–36 months, who had recovered from IPD, and age-matched healthy controls and vaccinated them with 1 dose of the 23-valent PPV to mimic natural exposure. We collected serum samples after vaccination and analysed the dynamics of anti-polysaccharide antibody responses to several capsular antigens. Mean IgG response times to different serotypes were 6.4–7.3 days, with standard deviations of 0.9–1.85 days, suggesting a natural range in response times of up to 7 days. Serotype 1 elicited the largest fold-rise, serotype 23F the smallest. The proportion of responses achieved by day 7 was similar in children with a history of IPD and healthy children. There was considerable natural variation in the rapidity of anti-capsular IgG responses extending over 4–7 days. There was no evidence to suggest that children who have experienced IPD respond more slowly to heterologous pneumococcal capsular antigens than do healthy children.
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Reeves SL, Jary HK, Gondhi JP, Kleyn M, Wagner AL, Dombkowski KJ. Pneumococcal vaccination coverage among children with sickle cell anemia, sickle cell trait, and normal hemoglobin. Pediatr Blood Cancer 2018; 65:e27282. [PMID: 29905397 DOI: 10.1002/pbc.27282] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Revised: 05/02/2018] [Accepted: 05/15/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND Children with sickle cell anemia and sickle cell trait are at an increased risk of invasive pneumococcal disease compared to children with normal hemoglobin. We assessed and compared pneumococcal vaccination status among these three groups. PROCEDURE Children with sickle cell anemia and sickle cell trait were identified using Michigan newborn screening records (1997-2014); each child was matched to four children with normal hemoglobin based on age, Medicaid enrollment (at least 1 year from 2012-2014), race, and census tract. Vaccination records were obtained from the state's immunization system. Pneumococcal vaccine coverage (PCV7 or PCV13 depending on date of administration) was assessed at milestone ages of 3, 5, 7, and 16 months. The proportion of children with vaccine coverage at each milestone was calculated overall and compared among children with sickle cell anemia, sickle cell trait, and normal hemoglobin using chi-square tests. RESULTS The study population consisted of 355 children with sickle cell anemia, 17,319 with sickle cell trait, and 70,757 with normal hemoglobin. The proportion of children with age-appropriate pneumococcal vaccination coverage was low at each milestone and generally decreased over time. Children with sickle cell anemia were more likely to be covered compared to children with sickle cell trait or normal hemoglobin. CONCLUSIONS Despite higher pneumococcal vaccination coverage among children with sickle cell anemia, opportunities for improvement exist among all children. Targeted interventions will benefit from mechanisms to identify children with increased risks such as sickle cell anemia or trait to improve pneumococcal vaccination coverage among these groups.
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Affiliation(s)
- Sarah L Reeves
- Child Health Evaluation and Research Center, University of Michigan, Ann Arbor, Michigan
| | - Hannah K Jary
- Child Health Evaluation and Research Center, University of Michigan, Ann Arbor, Michigan
| | - Jennifer P Gondhi
- Child Health Evaluation and Research Center, University of Michigan, Ann Arbor, Michigan
| | - Mary Kleyn
- Michigan Department of Health and Human Services, Lansing, Michigan
| | - Abram L Wagner
- Department of Epidemiology, University of Michigan, Ann Arbor, Michigan
| | - Kevin J Dombkowski
- Child Health Evaluation and Research Center, University of Michigan, Ann Arbor, Michigan
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Woll C, Neuman MI, Pruitt CM, Wang ME, Shapiro ED, Shah SS, McCulloh RJ, Nigrovic LE, Desai S, DePorre AG, Leazer RC, Marble RD, Balamuth F, Feldman EA, Sartori L, Browning WL, Aronson PL. Epidemiology and Etiology of Invasive Bacterial Infection in Infants ≤60 Days Old Treated in Emergency Departments. J Pediatr 2018; 200:210-217.e1. [PMID: 29784512 PMCID: PMC6109608 DOI: 10.1016/j.jpeds.2018.04.033] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 04/07/2018] [Accepted: 04/17/2018] [Indexed: 01/11/2023]
Abstract
OBJECTIVES To help guide empiric treatment of infants ≤60 days old with suspected invasive bacterial infection by describing pathogens and their antimicrobial susceptibilities. STUDY DESIGN Cross-sectional study of infants ≤60 days old with invasive bacterial infection (bacteremia and/or bacterial meningitis) evaluated in the emergency departments of 11 children's hospitals between July 1, 2011 and June 30, 2016. Each site's microbiology laboratory database or electronic medical record system was queried to identify infants from whom a bacterial pathogen was isolated from either blood or cerebrospinal fluid. Medical records of these infants were reviewed to confirm the presence of a pathogen and to obtain demographic, clinical, and laboratory data. RESULTS Of the 442 infants with invasive bacterial infection, 353 (79.9%) had bacteremia without meningitis, 64 (14.5%) had bacterial meningitis with bacteremia, and 25 (5.7%) had bacterial meningitis without bacteremia. The peak number of cases of invasive bacterial infection occurred in the second week of life; 364 (82.4%) infants were febrile. Group B streptococcus was the most common pathogen identified (36.7%), followed by Escherichia coli (30.8%), Staphylococcus aureus (9.7%), and Enterococcus spp (6.6%). Overall, 96.8% of pathogens were susceptible to ampicillin plus a third-generation cephalosporin, 96.0% to ampicillin plus gentamicin, and 89.2% to third-generation cephalosporins alone. CONCLUSIONS For most infants ≤60 days old evaluated in a pediatric emergency department for suspected invasive bacterial infection, the combination of ampicillin plus either gentamicin or a third-generation cephalosporin is an appropriate empiric antimicrobial treatment regimen. Of the pathogens isolated from infants with invasive bacterial infection, 11% were resistant to third-generation cephalosporins alone.
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Affiliation(s)
- Christopher Woll
- Departments of Pediatrics and of Emergency Medicine, Section of Pediatric Emergency Medicine, Yale School of Medicine, New Haven, CT
| | - Mark I. Neuman
- Division of Emergency Medicine, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Christopher M. Pruitt
- Division of Pediatric Emergency Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL
| | - Marie E. Wang
- Division of Pediatric Hospital Medicine, Department of Pediatrics, Lucile Packard Children’s Hospital Stanford, Stanford University School of Medicine, Palo Alto, CA
| | - Eugene D. Shapiro
- Departments of Pediatrics, of Epidemiology, and of Investigative Medicine, Yale University, New Haven, CT
| | - Samir S. Shah
- Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH,Division of Hospital Medicine, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
| | - Russell J. McCulloh
- Division of Infectious Diseases, Children’s Mercy Hospital, Kansas City, MO,Division of Hospital Medicine, Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO
| | - Lise. E. Nigrovic
- Division of Emergency Medicine, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, MA
| | - Sanyukta Desai
- Division of Hospital Medicine, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
| | - Adrienne G. DePorre
- Division of Hospital Medicine, Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO
| | - Rianna C. Leazer
- Division of Hospital Medicine, Children's Hospital of The King's Daughters, Norfolk, Virginia
| | - Richard D. Marble
- Division of Emergency Medicine, Ann and Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Frances Balamuth
- Division of Emergency Medicine and Center for Pediatric Clinical Effectiveness, Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | | | - Laura Sartori
- Divisions of Pediatric Emergency Medicine, Vanderbilt University School of Medicine, Nashville, TN
| | - Whitney L. Browning
- Hospital Medicine, Department of Pediatrics, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Vanderbilt University School of Medicine, Nashville, TN
| | - Paul L. Aronson
- Departments of Pediatrics and of Emergency Medicine, Section of Pediatric Emergency Medicine, Yale School of Medicine, New Haven, CT,Address Correspondence to: Paul L. Aronson, MD, Section of Pediatric Emergency Medicine, Yale School of Medicine, 100 York Street, Suite 1F, New Haven, CT, 06511. Phone: 203-785-3849, Fax: 203-737-7447,
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50
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Olarte L, Barson WJ, Bradley JS, Tan TQ, Lin PL, Romero JR, Givner LB, Hoffman JA, Hultén KG, Mason EO, Kaplan SL. Invasive Pneumococcal Disease in Infants Aged 0-60 Days in the United States in the 13-Valent Pneumococcal Conjugate Vaccine Era. J Pediatric Infect Dis Soc 2018; 7:249-252. [PMID: 28510699 DOI: 10.1093/jpids/pix034] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 04/11/2017] [Indexed: 11/14/2022]
Abstract
We identified 53 infants aged 0-60 days with invasive pneumococcal disease (IPD) at 8 children's hospitals in the United States (2005-2015). After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13), IPD caused by PCV13 serotypes decreased ~30% providing some evidence of indirect protection. However, approximately 60% of IPD was still caused by PCV13 serotypes.
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Affiliation(s)
- Liset Olarte
- Pediatric Infectious Diseases Section, Baylor College of Medicine, Houston, Texas
| | - William J Barson
- Pediatric Infectious Diseases Section, Ohio State University College of Medicine, Columbus
| | - John S Bradley
- Pediatric Infectious Diseases Section, Rady Children's Hospital San Diego, California
| | - Tina Q Tan
- Pediatric Infectious Diseases Section, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Philana Ling Lin
- Pediatric Infectious Diseases Section, University of Pittsburgh School of Medicine, Pennsylvania
| | - José R Romero
- Pediatric Infectious Diseases Section, University of Arkansas for Medical Sciences, Little Rock
| | - Laurence B Givner
- Pediatric Infectious Diseases Section, Wake Forest University School of Medicine, Winston-Salem, North Carolina
| | - Jill A Hoffman
- Pediatric Infectious Diseases Section, Keck School of Medicine of the University of Southern California School of Medicine, Los Angeles
| | - Kristina G Hultén
- Pediatric Infectious Diseases Section, Baylor College of Medicine, Houston, Texas
| | - Edward O Mason
- Pediatric Infectious Diseases Section, Baylor College of Medicine, Houston, Texas
| | - Sheldon L Kaplan
- Pediatric Infectious Diseases Section, Baylor College of Medicine, Houston, Texas
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