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Zhang W, Bai P, Hu W. A narrative review on the effectiveness of PPSV23 vaccination in adults in China. Hum Vaccin Immunother 2025; 21:2440955. [PMID: 40099896 DOI: 10.1080/21645515.2024.2440955] [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: 08/20/2024] [Revised: 11/22/2024] [Accepted: 12/07/2024] [Indexed: 03/20/2025] Open
Abstract
Pneumococcal Polysaccharide Vaccine (PPSV23) is available for free in some Chinese cities for elderly patients and those with comorbidities. However, there is a lack of studies summarizing its preventive effect specifically in Chinese adults. This review aims to discuss the epidemiology of pneumococcal disease, coverage and effectiveness of PPSV23 vaccination, elderly individuals and patients with comorbidities, coadministration of PPSV23 vaccine with other vaccines, and future directions for its use in China. It was found that the PPSV23 vaccination rate among the elderly ranged from 1.2% to 42.1% depending on location, with an effectiveness of 9.34%(95%CI: 2.05%, 16.62%) to 57.7%(95%CI: 20.7%, 77.5%). There is a need to raise awareness of pneumococcal disease and its prevention, especially in China. To better manage pneumococcal disease in China, developing new vaccines for common serotypes and continuously monitoring serotype distribution associated with the disease is also needed.
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Affiliation(s)
- Weiyan Zhang
- Shandong Provincial Center for Disease Control and Prevention, Jinan, Shandong, China
| | - Peng Bai
- Value & Implementation Global Medical & Scientific Affairs, MSD China, Shanghai, Jiangsu, China
| | - Weijun Hu
- Shaanxi Provincial Center for Disease Control and Prevention, Xi'an, Shaanxi, China
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Ramos B, Vadlamudi NK, Han C, Sadarangani M. Future immunisation strategies to prevent Streptococcus pneumoniae infections in children and adults. THE LANCET. INFECTIOUS DISEASES 2025:S1473-3099(24)00740-0. [PMID: 40112854 DOI: 10.1016/s1473-3099(24)00740-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 09/28/2024] [Accepted: 10/29/2024] [Indexed: 03/22/2025]
Abstract
Streptococcus pneumoniae is a major respiratory pathogen, causing 1·2 million deaths and 197 million pneumonia episodes globally in 2016. The spread of S pneumoniae to sterile sites, such as the blood and brain, leads to invasive pneumococcal disease. The best approach available for prevention of invasive pneumococcal disease in children and, more recently, adults is the use of pneumococcal conjugate vaccines (PCVs). PCVs are also highly effective at preventing colonisation and, thus, transmission, offering indirect protection to non-target immunisation groups such as adults-a characteristic that has been crucial in their success. However, PCVs only include and protect up to 20 of the 100 serotypes that can cause disease. The rise in adult cases of invasive pneumococcal disease from serotypes included in PCVs suggests indirect protection might be limited. Additionally, non-vaccine serotypes and some vaccine types that persist, some linked to antibiotic resistance, continue to cause disease. Future vaccine strategies include increasing the number of serotypes covered in PCVs for use in children and adults, broader vaccine use in adults, the development of adult-specific conjugate vaccines containing serotypes different from those covered in PCVs used in children, and protein vaccines, all of which will be explored in this Review. These strategies are expected to help mitigate the global burden of invasive pneumococcal disease in future years.
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Affiliation(s)
- Bernice Ramos
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada; Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Nirma Khatri Vadlamudi
- Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Crystal Han
- Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Manish Sadarangani
- Vaccine Evaluation Center, BC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
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Mancinetti F, Marinelli A, Boccardi V, Mecocci P. Challenges of infectious diseases in older adults: From immunosenescence and inflammaging through antibiotic resistance to management strategies. Mech Ageing Dev 2024; 222:111998. [PMID: 39447983 DOI: 10.1016/j.mad.2024.111998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 10/09/2024] [Accepted: 10/14/2024] [Indexed: 10/26/2024]
Abstract
Infectious diseases in older adults present a significant challenge to the healthcare system, marked by increased morbidity, mortality, and rising costs of care. Age-related changes (ARCs) in the immune system, including immunosenescence and inflammaging, contribute to heightened susceptibility to severe infections and reduced vaccine responsiveness. Additionally, alterations in the normal microbial flora due to aging and factors such as antibiotic therapy predispose older individuals to infections and age-related diseases. Changes in body composition also affect the pharmacokinetics and pharmacodynamics of drugs, complicating the management of antibiotics and leading to potential overdoses, adverse drug reactions, or underdoses that foster antibiotic resistance. The inappropriate use of antibiotics has exacerbated the emergence of multidrug-resistant pathogens, posing a critical global concern. This narrative review provides an overview of immunosenescence and inflammaging and focuses on three major infectious diseases affecting older adults: bacterial pneumonia, urinary tract infections, and Clostridium difficile infections. Through this exploration, we aim to highlight the need for targeted approaches in managing infectious diseases in the aging population.
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Affiliation(s)
- Francesca Mancinetti
- Division of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia-Santa Maria della Misericordia Hospital, Perugia, Italy
| | - Anna Marinelli
- Clinical of Internal Medicine, Department of Medical Surgical and Health Science, University of Trieste, Cattinara Hospital, Trieste, Italy
| | - Virginia Boccardi
- Division of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia-Santa Maria della Misericordia Hospital, Perugia, Italy.
| | - Patrizia Mecocci
- Division of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia-Santa Maria della Misericordia Hospital, Perugia, Italy; Division of Clinical Geriatrics, NVS Department, Karolinska Institutet, Stockholm, Sweden
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Xu Y, Ding Y, Wu H, Li D, Li Y, Hu Y, Meng H. Glycyrrhetinic acid reduces lung inflammation caused by pneumococcal infection by reducing the toxicity of pneumolysin. Heliyon 2024; 10:e38611. [PMID: 39397991 PMCID: PMC11471213 DOI: 10.1016/j.heliyon.2024.e38611] [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: 06/30/2024] [Revised: 09/26/2024] [Accepted: 09/26/2024] [Indexed: 10/15/2024] Open
Abstract
Objective In this study, to provide new methods for the treatment of Streptococcus pneumoniae infection, we aimed to describe the anti-inflammatory and antibacterial value of glycyrrhetinic acid on the basis of its inhibitory effect on bacterial growth (without killing the bacteria) and its reduction of the toxicity of S. pneumoniae. Methods A mouse model was established via intranasal administration of Streptococcus pneumoniae D39, and glycyrrhetinic acid was subcutaneously injected for treatment. The wet‒dry ratio, bacterial flora content and inflammatory factor levels in the mouse lungs were determined. Cell experiments were used to evaluate glycyrrhetinic acid-mediated inhibition of PLY hemolysis and A549 cell death, and WB was used to measure glycyrrhetinic acid-mediated inhibition of PLY oligomerization. Results Glycyrrhetinic acid reduced the levels of inflammatory factors, the dry‒wet ratio, the abundance of S. pneumoniae in the lungs of infected mice, pneumolysin-mediated A549 cell death, erythrocyte hemolysis and PLY oligoplasia. Conclusion Glycyrrhetinic acid can reduce the virulence of S. pneumoniae by preventing the oligomerization of PLY.
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Affiliation(s)
- Yan Xu
- Department of Pediatrics, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, China
- School of Pediatrics, Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, China
| | - Ying Ding
- Department of Pediatrics, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, China
- School of Pediatrics, Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, China
| | - Hongji Wu
- Department of Pediatrics, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, China
| | - Donglin Li
- Department of Pediatrics, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, China
| | - Yudi Li
- Department of Pediatrics, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, China
| | - Yibo Hu
- Department of Pediatrics, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, China
| | - Haoji Meng
- Department of Pediatrics, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, China
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Doherty K, Bonnett L, Agbla SC, Beveridge NER, Decraene V, Fleming KM, Hungerford D, French N. The effectiveness of revaccination with pneumococcal polysaccharide vaccine for preventing pneumococcal disease in older adults in England: A population-based cohort study. Vaccine 2024; 42:126002. [PMID: 38796329 DOI: 10.1016/j.vaccine.2024.05.050] [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: 03/08/2024] [Revised: 05/09/2024] [Accepted: 05/21/2024] [Indexed: 05/28/2024]
Abstract
BACKGROUND Pneumococcal disease in older adults in the United Kingdom is rising despite immunisation. A key gap in the literature is the clinical effectiveness of revaccination with the pneumococcal polysaccharide vaccine (PPV23). METHODS A cohort study was performed in England, using electronic medical records in the Clinical Practice Research Datalink. Individuals aged ≥64 years and vaccinated with PPV23 were included. Rates of hospitalised pneumonia (HP) and invasive pneumococcal disease (IPD) were compared between individuals receiving a single PPV23 dose versus those receiving two doses using multi-level Cox proportional hazards models. Propensity score weighting was performed to minimise the effect of confounding covariates across the comparison groups. RESULTS Between 2006 and 2019, there were 462 505 eligible participants. Of those, 6747 (1·5 %) received revaccination. Two doses compared to one dose was associated with an increased risk of HP (adjusted Hazard Ratio [aHR] 1·95; 95 %CI 1·74-2·20) and IPD (aHR 1·44; 95 %CI 1·41-1·46). In participants aged 64-74 years PPV23 revaccination was associated with more IPD (aHR 2·02; 95 %CI 1·75-2·33) and HP (aHR 1·46; 95 %CI 1·42-1.49). In those aged ≥75 years PPV23 revaccination was associated with more HP (aHR 1·12; 95 %CI 1·08-1·16) with no statistically significant difference detected in risk of IPD (aHR 1·20; 95 %CI 0·94-1·52). CONCLUSIONS No clear benefit of PPV23 revaccination was measured in older adults in this observational study. The small proportion of revaccinated subjects limits the strength of the conclusions. Further research evaluating the clinical effectiveness of PPV23 revaccination is required.
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Affiliation(s)
- Klara Doherty
- Department of Clinical Infection and Microbiology and Immunology, Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Members of Liverpool Health Partners, L69 7BE Liverpool, UK; Royal Liverpool and Broadgreen University Hospitals NHS Trust, Members of Liverpool Health Partners, L7 8XP Liverpool, UK
| | - Laura Bonnett
- Department of Health Data Science, Institute of Population Health, University of Liverpool, Members of Liverpool Health Partners, Liverpool L69 3GL, UK
| | - Schadrac C Agbla
- Department of Health Data Science, Institute of Population Health, University of Liverpool, Members of Liverpool Health Partners, Liverpool L69 3GL, UK
| | - Natalie E R Beveridge
- Department of Clinical Infection and Microbiology and Immunology, Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Members of Liverpool Health Partners, L69 7BE Liverpool, UK; Royal Liverpool and Broadgreen University Hospitals NHS Trust, Members of Liverpool Health Partners, L7 8XP Liverpool, UK
| | - Valérie Decraene
- Department of Clinical Infection and Microbiology and Immunology, Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Members of Liverpool Health Partners, L69 7BE Liverpool, UK; Field Services, United Kingdom Health Security Agency, Liverpool L3 1DS, UK
| | - Kate M Fleming
- Department of Public Health, Policy & Systems, Institute of Population Health, University of Liverpool, Members of Liverpool Health Partners, Liverpool L69 3GL, UK
| | - Daniel Hungerford
- Department of Clinical Infection and Microbiology and Immunology, Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Members of Liverpool Health Partners, L69 7BE Liverpool, UK; National Institute for Health and Care Research Health Protection Research Unit in Gastrointestinal Infections at the University of Liverpool, Liverpool L69 3GL, UK
| | - Neil French
- Department of Clinical Infection and Microbiology and Immunology, Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Members of Liverpool Health Partners, L69 7BE Liverpool, UK; Royal Liverpool and Broadgreen University Hospitals NHS Trust, Members of Liverpool Health Partners, L7 8XP Liverpool, UK.
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da Costa Rodrigues T, Zorzete P, Miyaji EN, Gonçalves VM. Novel method for production and purification of untagged pneumococcal surface protein A from clade 1. Appl Microbiol Biotechnol 2024; 108:281. [PMID: 38570417 PMCID: PMC10990985 DOI: 10.1007/s00253-024-13098-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 02/19/2024] [Accepted: 02/28/2024] [Indexed: 04/05/2024]
Abstract
Streptococcus pneumoniae can cause diseases with high mortality and morbidity. The licensed vaccines are based on capsular polysaccharides and induce antibodies with low cross reactivity, leading to restricted coverage of serotypes. For surpassing this limitation, new pneumococcal vaccines are needed for induction of broader protection. One important candidate is the pneumococcal surface protein A (PspA), which can be classified in 6 clades and 3 families. We have reported an efficient process for production and purification of untagged recombinant PspA from clade 4 (PspA4Pro). We now aim to obtain a highly pure recombinant PspA from clade 1 (PspA1) to be included, together with PspA4Pro, in a vaccine formulation to broaden response against pneumococci. The vector pET28a-pspA1 was constructed and used to transform Escherichia coli BL21(DE3) strain. One clone with high production of PspA1 was selected and adapted to high-density fermentation (HDF) medium. After biomass production in 6 L HDF using a bioreactor, the purification was defined after testing 3 protocols. During the batch bioreactor cultivation, plasmid stability remained above 90% and acetate formation was not detected. The final protein purification process included treatment with a cationic detergent after lysis, anion exchange chromatography, cryoprecipitation, cation exchange chromatography, and multimodal chromatography. The final purification process showed PspA1 purity of 93% with low endotoxin content and an overall recovery above 20%. The novel established process can be easily scaled-up and proved to be efficient to obtain a highly pure untagged PspA1 for inclusion in vaccine formulations. KEY POINTS: • Purification strategy for recombinant PspA1 from Streptococcus pneumoniae • Downstream processing for untagged protein antigens, the case of PspA1 • Purification strategy for PspA variants relies on buried amino acids in their sequences.
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Affiliation(s)
- Tasson da Costa Rodrigues
- Laboratório de Bacteriologia, Instituto Butantan, São Paulo, São Paulo, Brazil
- Programa de Pós-Graduação Interunidades Em Biotecnologia, Universidade de São Paulo, São Paulo, São Paulo, Brazil
| | - Patricia Zorzete
- Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, São Paulo, Brazil
| | - Eliane Namie Miyaji
- Laboratório de Bacteriologia, Instituto Butantan, São Paulo, São Paulo, Brazil
- Programa de Pós-Graduação Interunidades Em Biotecnologia, Universidade de São Paulo, São Paulo, São Paulo, Brazil
| | - Viviane Maimoni Gonçalves
- Programa de Pós-Graduação Interunidades Em Biotecnologia, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
- Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, São Paulo, Brazil.
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Su L, Zhou X, Peng W, Luo J, Lin Q, Liu L, Lin J, Lin S, Zhang K, Chen H, Liu M. Investigation on the correlation factors of positive Streptococcus pneumoniae antibody and IgG antibody level of Streptococcus pneumoniae in the elderly over 60 years old in Shenzhen. Vaccine 2024; 42:2448-2454. [PMID: 38458872 DOI: 10.1016/j.vaccine.2024.01.070] [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: 05/31/2023] [Revised: 01/09/2024] [Accepted: 01/22/2024] [Indexed: 03/10/2024]
Abstract
BACKGROUND Pneumococcal Polysaccharide Vaccine (PPV-23), designed to protect against the most common serotype of Streptococcus pneumoniae, is intended to protect the elderly and other high-risk groups. However, the immunogenicity of all 23 pneumococcal polysaccharide vaccines in older adults has not been thoroughly studied. OBJECTIVE The purpose of this study is to look into the factors that influence the effect of the pneumonia vaccine on the elderly over 60 years old in Shenzhen, as well as their IgG antibody level against Streptococcus pneumoniae. METHODS To determine the immune effectiveness of pneumococcal vaccination in older adults over 60 years old, we used the 3rd generation enzyme-linked immunosorbent assay to detect the antibody level of older adults to all 23 pneumococcal polysaccharide vaccines following pneumococcal immunization. RESULTS Vaccination, the number of physical examinations, pneumonia knowledge, and the pneumonia vaccination policy of the elderly in Shenzhen were all positively correlated with Streptococcus pneumoniae antibody positivity. The distribution of subtypes did not differ between elderly adults (over 65) and younger adults (under 65). The GMCs of IgG antibodies to PPS were significantly lower in males than in females for types 7f, 18c and 19a. At the same time, we found that people with chronic respiratory disease have lower type 9n than people without chronic respiratory disease. Other chronic diseases, such as hypertension and diabetes, had no difference in subtype distribution. CONCLUSION There was a statistically significant difference in antibody positivity rates for older people with more frequent medical check-ups in Shenzhen, indicating that publicity is playing a role. The effects of age, gender, and chronic diseases on naturally acquired anti-PPS IgG differ.
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Affiliation(s)
- Lixian Su
- Shenzhen Futian District Maternal and Child Health Hospital, Shenzhen, China.
| | - Xiaofeng Zhou
- Shenzhen Longhua District Center for Disease Control and Prevention, Shenzhen, China.
| | - Weijun Peng
- Shenzhen Longhua District Center for Disease Control and Prevention, Shenzhen, China.
| | - Jingwei Luo
- Shenzhen Longhua District Center for Disease Control and Prevention, Shenzhen, China
| | - Qiaoxiang Lin
- Shenzhen Longhua District Center for Disease Control and Prevention, Shenzhen, China
| | - Lizhen Liu
- Shenzhen Longhua District Center for Disease Control and Prevention, Shenzhen, China
| | - Jian Lin
- Shenzhen Longhua District Center for Disease Control and Prevention, Shenzhen, China
| | - Shufen Lin
- Shenzhen Longhua District Center for Disease Control and Prevention, Shenzhen, China
| | - Kechun Zhang
- Shenzhen Longhua District Center for Disease Control and Prevention, Shenzhen, China
| | - Hongbiao Chen
- Shenzhen Longhua District Center for Disease Control and Prevention, Shenzhen, China.
| | - Muyun Liu
- National Engineering Research Center of Foundational Technologies for CGT Industy, Shenzhen, China; Shenzhen Kenuo Medical Lab, Nanshan, Shenzhen, China.
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Paróczai D, Burian K, Bikov A. Bacterial Vaccinations in Patients with Chronic Obstructive Pulmonary Disease. Vaccines (Basel) 2024; 12:213. [PMID: 38400196 PMCID: PMC10893474 DOI: 10.3390/vaccines12020213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 02/14/2024] [Accepted: 02/16/2024] [Indexed: 02/25/2024] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is a frequent, often progressive, chronic disease of the lungs. Patients with COPD often have impaired immunity; therefore, they are prone to chest infections, such as pneumonia or bronchitis. Acute exacerbations of COPD are major events that accelerate disease progression, contributing to its symptoms' burden, morbidity, and mortality. Both pneumonia and acute exacerbations in COPD are caused by bacteria against which there are effective vaccinations. Although the number of randomised controlled studies on bacterial vaccinations in COPD is limited, national and international guidelines endorse specific vaccinations in patients with COPD. This review will summarise the different types of vaccinations that prevent pneumonia and COPD exacerbations. We also discuss the results of early phase studies. We will mainly focus on Streptococcus pneumoniae, as this bacterium was predominantly investigated in COPD. However, we also review studies investigating vaccinations against Haemophilus influenzae, Moraxella catarrhalis, and Bordetella pertussis.
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Affiliation(s)
- Dóra Paróczai
- Department of Medical Microbiology, University of Szeged, H-6720 Szeged, Hungary; (D.P.); (K.B.)
- Albert Szent-Györgyi Health Center, Department of Pulmonology, University of Szeged, H-6720 Szeged, Hungary
| | - Katalin Burian
- Department of Medical Microbiology, University of Szeged, H-6720 Szeged, Hungary; (D.P.); (K.B.)
| | - Andras Bikov
- Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester M23 9LT, UK
- Division of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Manchester M13 9PL, UK
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Del Riccio M, Boccalini S, Cosma C, Vaccaro G, Bonito B, Zanella B, Salvati C, Giorgetti D, Rigon L, Biamonte MA, Monami M, Bonanni P, Bechini A. Effectiveness of pneumococcal vaccination on hospitalization and death in the adult and older adult diabetic population: a systematic review. Expert Rev Vaccines 2023; 22:1179-1184. [PMID: 37990793 DOI: 10.1080/14760584.2023.2286374] [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: 05/10/2023] [Accepted: 11/17/2023] [Indexed: 11/23/2023]
Abstract
INTRODUCTION Diabetic patients are at a higher risk of getting pneumococcal disease and are therefore recommended to get vaccinated. The aim of our systematic review is the retrieval and analysis of all available evidence on the effect of pneumococcal vaccination on the risk of hospitalization and death in adult patients with diabetes. RESEARCH DESIGN AND METHODS MEDLINEand EMBASE were searched from inception until January 2023. We included all studies investigating whether pneumococcal vaccination reduces the risk of dying or being hospitalized in diabetic patients. The Newcastle-Ottawa scale was used to assess risk of bias. RESULTS Only two studies, encompassing a total of 68,246 subjects, were considered eligible for inclusion and of high quality. In both studies polysaccharide pneumococcal vaccination was associated with a reduction of the risk of hospitalization or death in adult diabetic patients (aHR: 0.76 in one study, aOR: 0.97 in the other one). However, in neither of the two included studies the lower risk was statistically significant. CONCLUSIONS Further research is needed due to the potentially major clinical implications for diabetic patients. The results of this systematic review can serve as a foundation for future studies, indicating the importance of continuing research in this area to improve patient outcomes.
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Affiliation(s)
- Marco Del Riccio
- Department of Health Sciences, University of Florence, Firenze, Italy
| | - Sara Boccalini
- Department of Health Sciences, University of Florence, Firenze, Italy
| | - Claudia Cosma
- Medical School of Specialization in Hygiene and Preventive Medicine, University of Florence, Firenze, Italy
| | - Gabriele Vaccaro
- Medical School of Specialization in Hygiene and Preventive Medicine, University of Florence, Firenze, Italy
| | - Benedetta Bonito
- Department of Health Sciences, University of Florence, Firenze, Italy
| | - Beatrice Zanella
- Department of Health Sciences, University of Florence, Firenze, Italy
| | - Cristina Salvati
- Department of Health Sciences, University of Florence, Firenze, Italy
| | - Duccio Giorgetti
- Medical School of Specialization in Hygiene and Preventive Medicine, University of Florence, Firenze, Italy
| | - Lisa Rigon
- Medical School of Specialization in Hygiene and Preventive Medicine, University of Florence, Firenze, Italy
| | | | - Matteo Monami
- Diabetology, Careggi Hospital, University of Florence, Florence, Italy
| | - Paolo Bonanni
- Department of Health Sciences, University of Florence, Firenze, Italy
| | - Angela Bechini
- Department of Health Sciences, University of Florence, Firenze, Italy
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Musher DM, Anderson R, Feldman C. The remarkable history of pneumococcal vaccination: an ongoing challenge. Pneumonia (Nathan) 2022; 14:5. [PMID: 36153636 PMCID: PMC9509586 DOI: 10.1186/s41479-022-00097-y] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 08/22/2022] [Indexed: 11/21/2022] Open
Abstract
Although it varies with age and geographical distribution, the global burden of infection with Streptococcus pneumoniae (pneumococcus) remains considerable. The elderly, and younger adults with comorbid conditions, are at particularly high risk of pneumococcal infection, and this risk will increase as the population ages. Vaccination should be the backbone of our current strategies to deal with this infection. Main body: This manuscript reviews the history of the development of pneumococcal vaccines, and the impact of different vaccines and vaccination strategies over the past 111 years. It documents the early years of vaccine development in the gold mines of South Africa, when vaccination with killed pneumococci was shown to be effective, even before the recognition that different pneumococci were antigenically distinct. The development of type-specific vaccines, still with whole killed pneumococci, showed a high degree of efficacy. The identification of the importance of the pneumococcal capsule heralded the era of vaccination with capsular polysaccharides, although with the advent of penicillin, interest in pneumococcal vaccine development waned. The efforts of Austrian and his colleagues, who documented that despite penicillin therapy, patients still died from pneumococcal infection in the first 96 h, ultimately led to the licensing first of a 14-valent pneumococcal polysaccharide in 1977 followed by the 23-valent pneumococcal polysaccharide in 1983. The principal problem with these, as with other polysaccharide vaccines, was that that they failed to immunize infants and toddlers, who were at highest risk for pneumococcal disease. This was overcome by chemical linking or conjugation of the polysaccharide molecules to an immunogenic carrier protein. Thus began the era of pneumococcal conjugate vaccine (PCV), starting with PCV7, progressing to PCV10 and PCV13, and, most recently, PCV15 and PCV20. However, these vaccines remain serotype specific, posing the challenge of new serotypes replacing vaccine types. Current research addresses serotype-independent vaccines which, so far, has been a challenging and elusive endeavor. Conclusion: While there has been enormous progress in the development of pneumococcal vaccines during the past century, attempts to develop a vaccine that will retain its efficacy for most pneumococcal serotypes are ongoing.
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El‐Beyrouty C, Buckler R, Mitchell M, Phillips S, Groome S. Pneumococcal vaccination—A literature review and practice guideline update. Pharmacotherapy 2022; 42:724-740. [DOI: 10.1002/phar.2723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 06/21/2022] [Accepted: 06/27/2022] [Indexed: 11/08/2022]
Affiliation(s)
- Claudine El‐Beyrouty
- Department of Pharmacy Thomas Jefferson University Hospital Philadelphia Pennsylvania USA
| | - Rebecca Buckler
- Department of Pharmacy Thomas Jefferson University Hospital Philadelphia Pennsylvania USA
| | - Meghan Mitchell
- Department of Pharmacy Thomas Jefferson University Hospital Philadelphia Pennsylvania USA
| | - Samantha Phillips
- Department of Pharmacy Thomas Jefferson University Hospital Philadelphia Pennsylvania USA
| | - Sara Groome
- Department of Pharmacy Thomas Jefferson University Hospital Philadelphia Pennsylvania USA
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Tobuse AJ, Ang CW, Yeong KY. Modern vaccine development via reverse vaccinology to combat antimicrobial resistance. Life Sci 2022; 302:120660. [PMID: 35642852 DOI: 10.1016/j.lfs.2022.120660] [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: 03/25/2022] [Revised: 05/02/2022] [Accepted: 05/19/2022] [Indexed: 10/18/2022]
Abstract
With the continuous evolution of bacteria, the global antimicrobial resistance health threat is causing millions of deaths yearly. While depending on antibiotics as a primary treatment has its merits, there are no effective alternatives thus far in the pharmaceutical market against some drug-resistant bacteria. In recent years, vaccinology has become a key topic in scientific research. Combining with the growth of technology, vaccine research is seeing a new light where the process is made faster and more efficient. Although less discussed, bacterial vaccine is a feasible strategy to combat antimicrobial resistance. Some vaccines have shown promising results with good efficacy against numerous multidrug-resistant strains of bacteria. In this review, we aim to discuss the findings from studies utilizing reverse vaccinology for vaccine development against some multidrug-resistant bacteria, as well as provide a summary of multi-year bacterial vaccine studies in clinical trials. The advantages of reverse vaccinology in the generation of new bacterial vaccines are also highlighted. Meanwhile, the limitations and future prospects of bacterial vaccine concludes this review.
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Affiliation(s)
- Asuka Joy Tobuse
- School of Science, Monash University Malaysia Campus, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia
| | - Chee Wei Ang
- School of Science, Monash University Malaysia Campus, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia
| | - Keng Yoon Yeong
- School of Science, Monash University Malaysia Campus, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia.
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13
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Lee GC, Moreira AG, Hinojosa C, Benavides R, Winter C, Anderson AC, Chen CJ, Borsa N, Hastings G, Black CA, Bandy SM, Shaffer A, Restrepo MI, Ahuja SK. Metformin Attenuates Inflammatory Responses and Enhances Antibody Production in an Acute Pneumonia Model of Streptococcus pneumoniae. FRONTIERS IN AGING 2022; 3:736835. [PMID: 35821804 PMCID: PMC9261336 DOI: 10.3389/fragi.2022.736835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 04/06/2022] [Indexed: 01/09/2023]
Abstract
Metformin may potentially reverse various age-related conditions; however, it is unclear whether metformin can also mitigate or delay the deterioration of immunological resilience that occurs in the context of infections that are commonly observed in older persons. We examined whether metformin promotes the preservation of immunological resilience in an acute S. pneumoniae (SPN) infection challenge in young adult mice. Mice were fed metformin (MET-alone) or standard chow (controls-alone) for 10 weeks prior to receiving intratracheal inoculation of SPN. A subset of each diet group received pneumococcal conjugate vaccine at week 6 (MET + PCV and control + PCV). Compared to controls-alone, MET-alone had significantly less infection-associated morbidity and attenuated inflammatory responses during acute SPN infection. Metformin lowered the expression of genes in the lungs related to inflammation as well as shorter lifespan in humans. This was accompanied by significantly lower levels of pro-inflammatory cytokines (e.g., IL6). MET + PCV vs. control + PCV manifested enhanced SPN anticapsular IgM and IgG levels. The levels of SPN IgM production negatively correlated with expression levels of genes linked to intestinal epithelial structure among MET + PCV vs. control + PCV groups. Correspondingly, the gut microbial composition of metformin-fed mice had a significantly higher abundance in the Verrucomicrobia, Akkermansia muciniphila, a species previously associated with beneficial effects on intestinal integrity and longevity. Together, these findings indicate metformin's immunoprotective potential to protect against infection-associated declines in immunologic resilience.
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Affiliation(s)
- Grace C. Lee
- College of Pharmacy, The University of Texas at Austin, Austin, TX, United States
- Pharmacotherapy Education and Research Center, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
- The Foundation for Advancing Veterans’ Health Research, San Antonio, TX, United States
- Veterans Administration Research Center for AIDS and HIV-1 Infection and Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, TX, United States
| | - Alvaro G. Moreira
- Veterans Administration Research Center for AIDS and HIV-1 Infection and Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, TX, United States
- Department of Pediatrics, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
| | - Cecilia Hinojosa
- Department Pulmonary Diseases and Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
- South Texas Veterans Health Care System, San Antonio, TX, United States
| | - Raymond Benavides
- College of Pharmacy, The University of Texas at Austin, Austin, TX, United States
- Pharmacotherapy Education and Research Center, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
| | - Caitlyn Winter
- The Foundation for Advancing Veterans’ Health Research, San Antonio, TX, United States
- Veterans Administration Research Center for AIDS and HIV-1 Infection and Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, TX, United States
- Department of Pediatrics, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
| | - Audrey C. Anderson
- College of Pharmacy, The University of Texas at Austin, Austin, TX, United States
| | - Chang-Jui Chen
- College of Pharmacy, The University of Texas at Austin, Austin, TX, United States
| | - Noemi Borsa
- Department Pulmonary Diseases and Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
- South Texas Veterans Health Care System, San Antonio, TX, United States
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
- Internal Medicine Department, Respiratory Unit and Adult Cystic Fibrosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Gabrielyd Hastings
- Department Pulmonary Diseases and Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
- South Texas Veterans Health Care System, San Antonio, TX, United States
| | - Cody A. Black
- College of Pharmacy, The University of Texas at Austin, Austin, TX, United States
- Pharmacotherapy Education and Research Center, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
| | - Sarah M. Bandy
- College of Pharmacy, The University of Texas at Austin, Austin, TX, United States
- Pharmacotherapy Education and Research Center, School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
| | - Alexander Shaffer
- Department Pulmonary Diseases and Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
- South Texas Veterans Health Care System, San Antonio, TX, United States
| | - Marcos I. Restrepo
- Department Pulmonary Diseases and Critical Care Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
- South Texas Veterans Health Care System, San Antonio, TX, United States
| | - Sunil K. Ahuja
- Veterans Administration Research Center for AIDS and HIV-1 Infection and Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, TX, United States
- South Texas Veterans Health Care System, San Antonio, TX, United States
- Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
- Department of Microbiology, Immunology and Molecular Genetics, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
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Theilacker C, Fletcher MA, Jodar L, Gessner BD. PCV13 Vaccination of Adults against Pneumococcal Disease: What We Have Learned from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA). Microorganisms 2022; 10:127. [PMID: 35056576 PMCID: PMC8778913 DOI: 10.3390/microorganisms10010127] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 12/23/2021] [Accepted: 12/30/2021] [Indexed: 02/04/2023] Open
Abstract
The Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA) evaluated older adult pneumococcal vaccination and was one of the largest vaccine clinical trials ever conducted. Among older adults aged ≥65 years, the trial established 13-valent pneumococcal conjugate vaccine (PCV13) efficacy in preventing first episodes of bacteremic and nonbacteremic pneumococcal vaccine serotype (VT) community acquired pneumonia (CAP), and of vaccine serotype invasive pneumococcal disease (VT-IPD). Since the publication of the original trial results, 15 additional publications have extended the analyses. In this review, we summarize and integrate the full body of evidence generated by these studies, contextualize the results in light of their public health relevance, and discuss their implications for the assessment of current and future adult pneumococcal vaccination. This accumulating evidence has helped to better understand PCV13 efficacy, serotype-specific efficacy, efficacy in subgroups, the interpretation of immunogenicity data, and the public health value of adult PCV vaccination.
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Affiliation(s)
| | - Mark A. Fletcher
- Pfizer Emerging Markets, 23-25 Avenue du Docteur Lannelongue, 75014 Paris, France;
| | - Luis Jodar
- Pfizer Vaccines, 500 Arcola Rd., Collegeville, PA 19426, USA; (L.J.); (B.D.G.)
| | - Bradford D. Gessner
- Pfizer Vaccines, 500 Arcola Rd., Collegeville, PA 19426, USA; (L.J.); (B.D.G.)
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15
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Pneumococcal Vaccines: Past Findings, Present Work, and Future Strategies. Vaccines (Basel) 2021; 9:vaccines9111338. [PMID: 34835269 PMCID: PMC8620834 DOI: 10.3390/vaccines9111338] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 11/12/2021] [Accepted: 11/13/2021] [Indexed: 01/24/2023] Open
Abstract
The importance of Streptococcus pneumoniae has been well established. These bacteria can colonize infants and adults without symptoms, but in some cases can spread, invade other tissues and cause disease with high morbidity and mortality. The development of pneumococcal conjugate vaccines (PCV) caused an enormous impact in invasive pneumococcal disease and protected unvaccinated people by herd effect. However, serotype replacement is a well-known phenomenon that has occurred after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) and has also been reported for other PCVs. Therefore, it is possible that serotype replacement will continue to occur even with higher valence formulations, but the development of serotype-independent vaccines might overcome this problem. Alternative vaccines are under development in order to improve cost effectiveness, either using proteins or the pneumococcal whole cell. These approaches can be used as a stand-alone strategy or together with polysaccharide vaccines. Looking ahead, the next generation of pneumococcal vaccines can be impacted by the new technologies recently approved for human use, such as mRNA vaccines and viral vectors. In this paper, we will review the advantages and disadvantages of the addition of new polysaccharides in the current PCVs, mainly for low- and middle-income countries, and we will also address future perspectives.
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16
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Muri L, Ispasanie E, Schubart A, Thorburn C, Zamurovic N, Holbro T, Kammüller M, Pluschke G. Alternative Complement Pathway Inhibition Abrogates Pneumococcal Opsonophagocytosis in Vaccine-Naïve, but Not in Vaccinated Individuals. Front Immunol 2021; 12:732146. [PMID: 34707606 PMCID: PMC8543009 DOI: 10.3389/fimmu.2021.732146] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 09/23/2021] [Indexed: 01/19/2023] Open
Abstract
To assess the relative contribution of opsonisation by antibodies, classical and alternative complement pathways to pneumococcal phagocytosis, we analyzed killing of pneumococci by human blood leukocytes collected from vaccine-naïve and PCV13-vaccinated subjects. With serotype 4 pneumococci as model, two different physiologic opsonophagocytosis assays based on either hirudin-anticoagulated whole blood or on washed cells from EDTA-anticoagulated blood reconstituted with active serum, were compared. Pneumococcal killing was measured in the presence of inhibitors targeting the complement components C3, C5, MASP-2, factor B or factor D. The two assay formats yielded highly consistent and comparable results. They highlighted the importance of alternative complement pathway activation for efficient opsonophagocytic killing in blood of vaccine-naïve subjects. In contrast, alternative complement pathway inhibition did not affect pneumococcal killing in PCV13-vaccinated individuals. Independent of amplification by the alternative pathway, even low capsule-specific antibody concentrations were sufficient to efficiently trigger classical pathway mediated opsonophagocytosis. In heat-inactivated or C3-inhibited serum, high concentrations of capsule-specific antibodies were required to trigger complement-independent opsonophagocytosis. Our findings suggest that treatment with alternative complement pathway inhibitors will increase susceptibility for invasive pneumococcal infection in non-immune subjects, but it will not impede pneumococcal clearance in vaccinated individuals.
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Affiliation(s)
- Lukas Muri
- Molecular Immunology Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Emma Ispasanie
- Molecular Immunology Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland.,University of Basel, Basel, Switzerland
| | - Anna Schubart
- Translational Medicine-Preclinical Safety, Novartis Institutes for Biomedical Research, Basel, Switzerland
| | | | - Natasa Zamurovic
- Translational Medicine-Preclinical Safety, Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Thomas Holbro
- Novartis Pharma AG, Global Drug Development, Basel, Switzerland
| | - Michael Kammüller
- Translational Medicine-Preclinical Safety, Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Gerd Pluschke
- Molecular Immunology Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland.,University of Basel, Basel, Switzerland
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17
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Sun X, Guo X, Qiu J, Zhao G, Xu X, Wagner AL, Jiang H, Huang Z, Ren J, Ma X, Liang X, Yao Y, Wu J, Lu Y. Effectiveness of 23-Valent Pneumococcal Polysaccharide Vaccine Against Pneumococcal Diseases Among the Elderly Aged 60 Years or Older: A Matched Test Negative Case-Control Study in Shanghai, China. Front Public Health 2021; 9:620531. [PMID: 34616702 PMCID: PMC8488431 DOI: 10.3389/fpubh.2021.620531] [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: 10/23/2020] [Accepted: 08/23/2021] [Indexed: 11/23/2022] Open
Abstract
Background:Streptococcus pneumoniae infection among adults, especially in adults over 60 years old in China results in a large number of hospitalizations and a substantial financial burden. This study assessed the vaccine effectiveness (VE) of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal diseases among the elderly aged 60 years or older in Shanghai, China. Methods: We conducted a test-negative case–control study among the elderly aged 60 years or older who sought care at hospitals in 13 districts of Shanghai from September 14, 2013 to August 31, 2019. A case was defined as pneumococcal disease and testing positive for Streptococcus pneumoniae. Controls had symptoms congruent with pneumococcal disease but were negative for Streptococcus pneumoniae. We conducted 1:2 matching by gender, age, hospital and admission date. Vaccination status was verified from the immunization system database. VE was calculated with conditional logistic regression according to the formula (1–OR) ×100%. Results: Overall, 603 adults aged 60 years or older with pneumococcal disease and positive for Streptococcus pneumoniae were included as cases, and 19.6% (118 persons) had a recorded PPV23 vaccination. The controls included 1,206 adults, whose vaccination rate was 23.8% (287 persons). The VE against pneumococcal diseases among the whole population was 24% (95% CI: 2%, 40%) and among women 44% (95% CI: 6%, 67%). After adjusting for multiple variables, the effectiveness of PPV23 against pneumococcal diseases was still statistically significant with VE for all of 25% (95% CI: 3%, 42%) and VE for women of 49% (95% CI: 11%, 71%). Conclusion: PPV23 was effective against pneumococcal diseases in adults aged 60 years or older in Shanghai, China. Its relatively high effectiveness among women warrants this group to be particularly targeted for vaccination, with further research on why vaccination effectiveness is less among men.
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Affiliation(s)
- Xiaodong Sun
- Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
| | - Xiang Guo
- Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
| | - Jing Qiu
- Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
| | - Genming Zhao
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Xinxin Xu
- Shanghai Municipal Center for Health Promotion, Shanghai, China
| | - Abram L Wagner
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States
| | - Hongli Jiang
- Department of Health Economics, School of Public Health, Fudan University, Shanghai, China
| | - Zhuoying Huang
- Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
| | - Jia Ren
- Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
| | - Xiaoying Ma
- Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
| | - Xiufang Liang
- Yangpu District Center for Disease Control and Prevention, Shanghai, China
| | - Yao Yao
- Chongming District Center for Disease Control and Prevention, Shanghai, China
| | - Jialing Wu
- Songjiang District Center for Disease Control and Prevention, Shanghai, China
| | - Yihan Lu
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
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18
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Heo JY, Seo YB, Choi WS, Kim EJ, Jeong HW, Lee J, Yoon JG, Noh JY, Cheong HJ, Kim WJ, Song JY. Effectiveness of Pneumococcal Vaccination Against Hospitalized Pneumococcal Pneumonia in Older Adults: A Prospective, Test-Negative Study. J Infect Dis 2021; 225:836-845. [PMID: 34537847 DOI: 10.1093/infdis/jiab474] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 09/15/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Despite use of the 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) over the last decade, the disease burden of pneumococcal pneumonia is still high. We evaluated the field effectiveness of PCV13, PPSV23, and sequential vaccination against pneumococcal pneumonia in older adults. METHODS This prospective multicenter study was conducted in adults aged ≥ 65 years with hospitalized community-acquired pneumonia (CAP) between September 2015 and August 2017. The case-control test-negative design was used to estimate vaccine effectiveness (VE) against pneumococcal CAP. RESULTS Of 1,525 cases with hospitalized CAP, 167 (11.0%) were identified as pneumococcal CAP. In the elderly aged ≥65 years, the adjusted VE of pneumococcal vaccines against pneumococcal CAP was statistically insignificant: 40.0% (95% CI -10.8% to 67.5%) for PCV13 and 11.0% (95% CI, -26.4% to 37.3%) for PPSV23. However, in the younger subgroup (aged 65-74 years), sequential PCV13/PPSV23 vaccination showed the highest adjusted VE of 80.3% (95% CI 15.9% to 95.4%), followed by single-dose PCV13 (adjusted VE 66.4%; 95% CI 0.8% to 88.6%) and PPSV23 (adjusted VE 18.5%; 95% CI -38.6% to 52.0%). CONCLUSIONS Sequential PCV13/PPSV23 vaccination is most effective for preventing pneumococcal CAP among the elderly aged 65-74 years.
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Affiliation(s)
- Jung Yeon Heo
- Department of Infectious Diseases, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Yu Bin Seo
- Division of Infectious Disease, Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Won Suk Choi
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Eun Jin Kim
- Department of Infectious Diseases, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Hye Won Jeong
- Division of Infectious Diseases, Chungbuk National University College of Medicine, Cheongju, Chungcheongbuk-do, Republic of Korea
| | - Jacob Lee
- Division of Infectious Disease, Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Jin Gu Yoon
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Ji Yun Noh
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.,Asian Pacific Influenza Institute (APII), Korea University College of Medicine, Seoul, Republic of Korea
| | - Hee Jin Cheong
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.,Asian Pacific Influenza Institute (APII), Korea University College of Medicine, Seoul, Republic of Korea
| | - Woo Joo Kim
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.,Asian Pacific Influenza Institute (APII), Korea University College of Medicine, Seoul, Republic of Korea
| | - Joon Young Song
- Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.,Asian Pacific Influenza Institute (APII), Korea University College of Medicine, Seoul, Republic of Korea
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19
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Herta T, Bhattacharyya A, Rosolowski M, Conrad C, Gurtner C, Gruber AD, Ahnert P, Gutbier B, Frey D, Suttorp N, Hippenstiel S, Zahlten J. Krueppel-Like Factor 4 Expression in Phagocytes Regulates Early Inflammatory Response and Disease Severity in Pneumococcal Pneumonia. Front Immunol 2021; 12:726135. [PMID: 34589087 PMCID: PMC8473698 DOI: 10.3389/fimmu.2021.726135] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 08/25/2021] [Indexed: 11/13/2022] Open
Abstract
The transcription factor Krueppel-like factor (KLF) 4 fosters the pro-inflammatory immune response in macrophages and polymorphonuclear neutrophils (PMNs) when stimulated with Streptococcus pneumoniae, the main causative pathogen of community-acquired pneumonia (CAP). Here, we investigated the impact of KLF4 expression in myeloid cells such as macrophages and PMNs on inflammatory response and disease severity in a pneumococcal pneumonia mouse model and in patients admitted to hospital with CAP. We found that mice with a myeloid-specific knockout of KLF4 mount an insufficient early immune response with reduced levels of pro-inflammatory cytokines and increased levels of the anti-inflammatory cytokine interleukin (IL) 10 in bronchoalveolar lavage fluid and plasma and an impaired bacterial clearance from the lungs 24 hours after infection with S. pneumoniae. This results in higher rates of bacteremia, increased lung tissue damage, more severe symptoms of infection and reduced survival. Higher KLF4 gene expression levels in the peripheral blood of patients with CAP at hospital admission correlate with a favourable clinical presentation (lower sequential organ failure assessment (SOFA) score), lower serum levels of IL-10 at admission, shorter hospital stay and lower mortality or requirement of intensive care unit treatment within 28 days after admission. Thus, KLF4 in myeloid cells such as macrophages and PMNs is an important regulator of the early pro-inflammatory immune response and, therefore, a potentially interesting target for therapeutic interventions in pneumococcal pneumonia.
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Affiliation(s)
- Toni Herta
- Department of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Aritra Bhattacharyya
- Department of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Maciej Rosolowski
- Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany
| | - Claudia Conrad
- Department of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Corinne Gurtner
- Department of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany
| | - Achim D. Gruber
- Department of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany
| | - Peter Ahnert
- Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany
| | - Birgitt Gutbier
- Department of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Doris Frey
- Department of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Norbert Suttorp
- Department of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Stefan Hippenstiel
- Department of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Janine Zahlten
- Department of Infectious Diseases and Respiratory Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
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20
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Kobayashi K, Jo T, Mimura W, Suzukawa M, Ohshima N, Tanaka G, Akazawa M, Matsui H, Fushimi K, Yasunaga H, Nagase T, Nagai H. Interrupted time-series analyses of routine vaccination program for elderly pneumonia patients in Japan; an ecological study using aggregated nationwide inpatient data. Hum Vaccin Immunother 2021; 17:2661-2669. [PMID: 33877954 DOI: 10.1080/21645515.2021.1875760] [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: 10/21/2022] Open
Abstract
A national routine pneumococcal pneumonia immunization program started in Japan in 2014. It targeted the population aged ≥65 years and used a 23-valent pneumococcal polysaccharide vaccine; PPSV23. However, its effectiveness was not well defined because of the lack of a comprehensive database on the PPSV23 vaccination status of each subject. We used interrupted time-series analyses to assess the changes in the incidence and prognosis of elderly patients hospitalized for pneumonia before and after initiation of the program. First, we estimated the PPSV23 coverage rates in subjects aged ≥65 years based on the number of shipped PPSV23 syringes and the estimated population in each prefecture. The estimated coverage rates reached around 40% in 2014 for the 3 Tohoku prefectures, while those in the other prefectures remained below 20%. After the national routine immunization program started, the estimated coverage rate increased significantly in every prefecture and exceeded 40% in 2017. Next, we aggregated the data extracted from the Japanese Diagnosis Procedure Combination database from April 2011 through February 2017 for hospitalized pneumonia patients aged ≥65 years. The data included data from 655,746 patients, excluding those in the 3 Tohoku prefectures. Interrupted time-series analyses found no change in the incidence of hospitalized pneumonia patients and in-hospital mortality after the vaccination program, but there was a decrease in the in-hospital mortality of pneumonia patients with severe comorbidities defined by the modified Charlson comorbidity index. These results suggest an association between the vaccination program and an improved outcome in hospitalized elderly pneumonia patients with severe comorbidities in Japan.
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Affiliation(s)
- Koichi Kobayashi
- Department of Internal medicine, Yoshikawa Central General Hospital, Saitama, Japan.,Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, Tokyo, Japan
| | - Taisuke Jo
- Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.,Department of Respiratory Medicine, The University of Tokyo, Tokyo, Japan
| | - Wataru Mimura
- Department of Public Health and Epidemiology, Meiji Pharmaceutical University, Tokyo, Japan
| | - Maho Suzukawa
- Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, Tokyo, Japan
| | - Nobuharu Ohshima
- Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, Tokyo, Japan
| | - Goh Tanaka
- Department of Respiratory Medicine, The University of Tokyo, Tokyo, Japan
| | - Manabu Akazawa
- Department of Public Health and Epidemiology, Meiji Pharmaceutical University, Tokyo, Japan
| | - Hiroki Matsui
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hideo Yasunaga
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Takahide Nagase
- Department of Respiratory Medicine, The University of Tokyo, Tokyo, Japan
| | - Hideaki Nagai
- Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, Tokyo, Japan
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21
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Masuda T, Nakatani E, Shirai T, Akamatsu T, Tamura K, Takahashi S, Tanaka Y, Watanabe H, Endo Y, Suzuki T, Saigusa M, Yamamoto A, Morita S, Sato Y, Asada K. Effectiveness of a 23-valent pneumococcal polysaccharide vaccine for the prevention of pneumococcal pneumonia in the elderly with chronic respiratory diseases: a case-control study of a single center. BMC Pulm Med 2021; 21:123. [PMID: 33863300 PMCID: PMC8051051 DOI: 10.1186/s12890-021-01491-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 04/08/2021] [Indexed: 11/21/2022] Open
Abstract
Background The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in preventing pneumococcal pneumonia has been controversial. Methods To evaluate the effectiveness of the PPSV23 in elderly outpatients with chronic respiratory diseases, we carried out a case–control study, including 4128 outpatients aged ≥ 65 years, in the respiratory department. Results There were 320 vaccinated patients, of which 164 were diagnosed with pneumococcal pneumonia. The adjusted odds ratio was 0.39 (95% confidence interval (CI), 0.17 to 0.89). In the subsets consisting of age groups ≥ 70 and ≥ 75 years, the adjusted odds ratio (95% CI) was respectively 0.16 (0.04 to 0.67) and 0.15 (0.02 to 1.12). Conclusion This real-world study suggests that PPSV23 can be useful in preventing pneumococcal pneumonia in the elderly with chronic respiratory diseases. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-021-01491-w.
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Affiliation(s)
- Toshihiro Masuda
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1, Shizuoka, Japan
| | - Eiji Nakatani
- Division of Clinical Biostatistics, Research Support Center, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoi, Shizuoka, 420-8527, Japan. .,Graduate School of Public Health, Shizuoka Graduate University of Public Health, 4-27-2 Kitaando, Aoi-ku, Shizuoka, 420-0881, Japan.
| | - Toshihiro Shirai
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1, Shizuoka, Japan
| | - Taisuke Akamatsu
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1, Shizuoka, Japan
| | - Kanami Tamura
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1, Shizuoka, Japan
| | - Shingo Takahashi
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1, Shizuoka, Japan
| | - Yuko Tanaka
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1, Shizuoka, Japan
| | - Hirofumi Watanabe
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1, Shizuoka, Japan
| | - Yoshinari Endo
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1, Shizuoka, Japan
| | - Takahito Suzuki
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1, Shizuoka, Japan
| | - Mika Saigusa
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1, Shizuoka, Japan
| | - Akito Yamamoto
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1, Shizuoka, Japan
| | - Satoru Morita
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1, Shizuoka, Japan
| | - Yoko Sato
- Division of Clinical Biostatistics, Research Support Center, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoi, Shizuoka, 420-8527, Japan
| | - Kazuhiro Asada
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1, Shizuoka, Japan
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22
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Hutton DW, McCullough JS, Prosser L, Ye W, Herman WH, Zhang P, Pilishvili T, Pike J. Costs implications of pneumococcal vaccination of adults aged 30-60 with a recent diagnosis of diabetes. Vaccine 2021; 39:1333-1338. [PMID: 33494965 PMCID: PMC9018094 DOI: 10.1016/j.vaccine.2020.11.060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 09/30/2020] [Accepted: 11/23/2020] [Indexed: 10/22/2022]
Abstract
OBJECTIVE The 23-valent pneumococcal polysaccharide vaccine is routinely recommended for adults with diabetes, but little is known about adherence to this recommendation and how vaccination of these adults affects costs related to pneumococcal disease. RESEARCH DESIGN AND METHODS We used data from a commercial insurance claims dataset to examine a cohort of non-elderly adults with a new diagnosis of diabetes and adults with no diagnosis of diabetes from 2005 to 2014. We examined rates of pneumococcal polysaccharide vaccination and the relationship between vaccination and pneumococcal disease costs, comparing results for persons with a diagnosis of diabetes and those with no diagnosis of diabetes. RESULTS Overall rates of pneumococcal polysaccharide vaccination among adults 30-60 years old were <1%/year. Rates of pneumococcal polysaccharide vaccination were higher for adults with diabetes. Pneumococcal polysaccharide vaccination rates more than doubled from 2.9% per year in 2005 to 6.0% per year in 2014 for adults vaccinated during the same year as their diabetes diagnosis. Using a two-part differences-in-differences model on a propensity-score matched dataset, pneumococcal polysaccharide vaccination may reduce average annual per-person pneumococcal disease costs by $90.54 [95% CI: $183.59, -$2.49, (p = 0.056)] in persons with diabetes from two years before to two years after vaccination. CONCLUSIONS Non-elderly adults with diabetes have low but rising rates of pneumococcal polysaccharide vaccination. Pneumococcal polysaccharide vaccination has a modest impact reducing overall costs of pneumococcal disease in this population.
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Affiliation(s)
- David W Hutton
- Department of Health Management and Policy, University of Michigan, United States.
| | - Jeffrey S McCullough
- Department of Health Management and Policy, University of Michigan, United States
| | - Lisa Prosser
- Department of Health Management and Policy, University of Michigan, United States; Department of Pediatrics and Communicable Diseases, University of Michigan, United States
| | - Wen Ye
- Department of Biostatistics, University of Michigan, United States
| | - William H Herman
- Departments of Internal Medicine and Epidemiology, University of Michigan, United States
| | - Ping Zhang
- Centers for Disease Control and Prevention, United States
| | | | - Jamison Pike
- Centers for Disease Control and Prevention, United States
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23
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Su WJ, Chuang PH, Chang LY, Lo HY, Chiang CS, Wang ET, Yang CH. Application of the screening and indirect cohort methods to evaluate the effectiveness of pneumococcal vaccination program in adults 75 years and older in Taiwan. BMC Infect Dis 2021; 21:45. [PMID: 33423657 PMCID: PMC7798272 DOI: 10.1186/s12879-020-05721-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 12/18/2020] [Indexed: 11/23/2022] Open
Abstract
Background The Taiwanese national 23-valent pneumococcal polysaccharide vaccine (PPV23) program in adults ≥75 years of age and the 13-valent pneumococcal conjugate vaccine (PCV13) program for children were implemented in 2008 and 2013, respectively. In this study we evaluated PPV23 vaccine effectiveness (PPV23VE) in the elderly, with regard to both direct protection from the vaccine itself and the indirect protection conferred by PCV13 immunization in children. Methods The incidence of invasive pneumococcal disease (IPD) in Taiwan from July 2008 to June 2016 was collected from IPD surveillance data. A comparison of IPD incidence with a nationwide vaccination registry allowed an estimation of PPV23VE by the screening and indirect cohort methods. Results The incidence of IPD in adults ≥75 years of age ranged from 13.9 per 100,000 inhabitants during the period July 2008–June 2013 to 10.4 per 100,000 inhabitants between July 2013 and June 2016 (relative risk [RR]: 0.75; 95% confidence interval [95% CI]: 0.67–0.85). According to the screening method, PPV23VE against death within 30 days of IPD onset, all IPD, and PPV23-serotype IPD was 32.5% (95% CI: 17.5–44.7%), 33.9% (95% CI: 25.2–41.5%) and 43.4% (95% CI: 34.4–51.2%), respectively. PPV23VE with the indirect cohort method was 39.0% (95% CI: 15.5–55.9%) for all PPV23 serotypes and 71.5% (95% CI: 44.2–85.4%) for 11 serotypes included in PPV23 but not in PCV13. During the period July 2008–June 2012, PPV23VE against PPV23-serotype IPD was 55.1% (95% CI: 27.2–72.3%). Conclusions PPV23 is able to prevent IPD and 30-day fatality in adults 75 years of age and older due to a combination of direct effects from PPV23 and indirect effects from PCV13. It might confer higher protection against PPV23-serotype IPD before the introduction of PCV13 program in children. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-020-05721-0.
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Affiliation(s)
- Wei-Ju Su
- Division of Acute Infectious Diseases, Centers for Disease Control, Ministry of Health and Welfare, 6, Linsen South Road, Taipei, 100, Taiwan, Republic of China.,Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
| | - Pei-Hung Chuang
- Center for Prevention and Treatment of Occupational Injury and Diseases, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.,Division of Clinical Toxicology and Occupational Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
| | - Luan-Yin Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
| | - Hsiu-Yun Lo
- Division of Acute Infectious Diseases, Centers for Disease Control, Ministry of Health and Welfare, 6, Linsen South Road, Taipei, 100, Taiwan, Republic of China
| | - Chuen-Sheue Chiang
- Division of Acute Infectious Diseases, Centers for Disease Control, Ministry of Health and Welfare, 6, Linsen South Road, Taipei, 100, Taiwan, Republic of China
| | - Ez-Tzu Wang
- Division of Acute Infectious Diseases, Centers for Disease Control, Ministry of Health and Welfare, 6, Linsen South Road, Taipei, 100, Taiwan, Republic of China
| | - Chin-Hui Yang
- Division of Acute Infectious Diseases, Centers for Disease Control, Ministry of Health and Welfare, 6, Linsen South Road, Taipei, 100, Taiwan, Republic of China.
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24
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Lawrence H, Pick H, Baskaran V, Daniel P, Rodrigo C, Ashton D, Edwards-Pritchard RC, Sheppard C, Eletu SD, Litt D, Fry NK, Rose S, Trotter C, McKeever TM, Lim WS. Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against vaccine serotype pneumococcal pneumonia in adults: A case-control test-negative design study. PLoS Med 2020; 17:e1003326. [PMID: 33095759 PMCID: PMC7584218 DOI: 10.1371/journal.pmed.1003326] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 08/31/2020] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV23) is available in the United Kingdom to adults aged 65 years or older and those in defined clinical risk groups. We evaluated the vaccine effectiveness (VE) of PPV23 against vaccine-type pneumococcal pneumonia in a cohort of adults hospitalised with community-acquired pneumonia (CAP). METHODS AND FINDINGS Using a case-control test-negative design, a secondary analysis of data was conducted from a prospective cohort study of adults (aged ≥16 years) with CAP hospitalised at 2 university teaching hospitals in Nottingham, England, from September 2013 to August 2018. The exposure of interest was PPV23 vaccination at any time point prior to the index admission. A case was defined as PPV23 serotype-specific pneumococcal pneumonia and a control as non-PPV23 serotype pneumococcal pneumonia or nonpneumococcal pneumonia. Pneumococcal serotypes were identified from urine samples using a multiplex immunoassay or from positive blood cultures. Multivariable logistic regression was used to derive adjusted odds of case status between vaccinated and unvaccinated individuals; VE estimates were calculated as (1 - odds ratio) × 100%. Of 2,357 patients, there were 717 PPV23 cases (48% vaccinated) and 1,640 controls (54.5% vaccinated). The adjusted VE (aVE) estimate against PPV23 serotype disease was 24% (95% CI 5%-40%, p = 0.02). Estimates were similar in analyses restricted to vaccine-eligible patients (n = 1,768, aVE 23%, 95% CI 1%-40%) and patients aged ≥65 years (n = 1,407, aVE 20%, 95% CI -5% to 40%), but not in patients aged ≥75 years (n = 905, aVE 5%, 95% CI -37% to 35%). The aVE estimate in relation to PPV23/non-13-valent pneumococcal conjugate vaccine (PCV13) serotype pneumonia (n = 417 cases, 43.7% vaccinated) was 29% (95% CI 6%-46%). Key limitations of this study are that, due to high vaccination rates, there was a lack of power to reject the null hypothesis of no vaccine effect, and that the study was not large enough to allow robust subgroup analysis in the older age groups. CONCLUSIONS In the setting of an established national childhood PCV13 vaccination programme, PPV23 vaccination of clinical at-risk patient groups and adults aged ≥65 years provided moderate long-term protection against hospitalisation with PPV23 serotype pneumonia. These findings suggest that PPV23 vaccination may continue to have an important role in adult pneumococcal vaccine policy, including the possibility of revaccination of older adults.
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Affiliation(s)
- Hannah Lawrence
- Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
- Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom
| | - Harry Pick
- Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
| | - Vadsala Baskaran
- Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
- Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom
- NIHR Nottingham Biomedical Research Centre, Queen’s Medical Centre, Nottingham, United Kingdom
| | - Priya Daniel
- Department of Respiratory Medicine, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, United Kingdom
| | - Chamira Rodrigo
- Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
| | - Deborah Ashton
- Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
| | | | - Carmen Sheppard
- Respiratory and Vaccine Preventable Bacteria Reference Unit, Public Health England–National Infection Service, Colindale, London, United Kingdom
| | - Seyi D. Eletu
- Respiratory and Vaccine Preventable Bacteria Reference Unit, Public Health England–National Infection Service, Colindale, London, United Kingdom
| | - David Litt
- Respiratory and Vaccine Preventable Bacteria Reference Unit, Public Health England–National Infection Service, Colindale, London, United Kingdom
| | - Norman K. Fry
- Respiratory and Vaccine Preventable Bacteria Reference Unit, Public Health England–National Infection Service, Colindale, London, United Kingdom
- Immunisation and Countermeasures Division, Public Health England Colindale–National Infection Service, London, United Kingdom
| | - Samuel Rose
- Respiratory and Vaccine Preventable Bacteria Reference Unit, Public Health England–National Infection Service, Colindale, London, United Kingdom
| | - Caroline Trotter
- Disease Dynamic Unit, Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Tricia M. McKeever
- Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom
- NIHR Nottingham Biomedical Research Centre, Queen’s Medical Centre, Nottingham, United Kingdom
| | - Wei Shen Lim
- Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
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25
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Weinberger DM, Shapiro ED. Pneumococcal Vaccines for Adults: What's Next? Clin Infect Dis 2020; 70:2493-2495. [PMID: 31402388 DOI: 10.1093/cid/ciz743] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 08/01/2019] [Indexed: 11/15/2022] Open
Affiliation(s)
- Daniel M Weinberger
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut
| | - Eugene D Shapiro
- Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut.,Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut
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26
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Huddar S, Park CM, Kim HJ, Jang S, Lee S. Discovery of 4-hydroxy-2-oxo-1,2-dihydroquinolines as potential inhibitors of Streptococcus pneumoniae, including drug-resistant strains. Bioorg Med Chem Lett 2020; 30:127071. [PMID: 32146051 DOI: 10.1016/j.bmcl.2020.127071] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 02/27/2020] [Accepted: 02/28/2020] [Indexed: 10/24/2022]
Abstract
New therapies for treating drug-resistant pneumococcal infections are urgently needed. The novel scaffold 6-hydroxy-4-oxo-1,2-dihydro-4H-quinoline was shown to have similar efficacies against all three different serotypes of S. pneumoniae, ATCC 49617™ (19F), ATCC BAA-1663™ (15B), and ATCC 700904™ (19A), in a resazurin-based high-throughput screen using the Korea Chemical Bank library. Further studies to identify a new lead with this scaffold, including tricyclic pyrrolo[3,2,1-ij]quinolone and pyrido[3,2,1-ij]quinolone derivatives, led to the identification of 6d, 7d and 12a. Compound 6d (IC50 = 0.92, 0.75, and 0.77 µM), 7d (IC50 = 0.57, 0.66, and 0.38 µM) and 12a (IC50 = 0.27, 1.03, and 0.62 µM) showed submicromolar IC50 values against 19F, 15B, and 19A, respectively, and thus serve as a starting point for further optimization. While some of compounds in this series exhibited acceptable pharmacokinetic profiles in preliminary in vivo rat experiments, the most active compound 12a showed poor solubility and high plasma protein binding. Our current research efforts are focused on optimizing compounds to improve physicochemical properties as well as potency.
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Affiliation(s)
- Srigouri Huddar
- Drug Information Platform Center, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea; Korea University of Science and Technology, Daejeon 34114, Republic of Korea
| | - Chul Min Park
- Center for Convergent Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea
| | - Hyung Jun Kim
- Discovery Biology Department, Antibacterial Resistance Research Laboratory, Institut Pasteur Korea, Seongnam 13488, Republic of Korea
| | - Soojin Jang
- Discovery Biology Department, Antibacterial Resistance Research Laboratory, Institut Pasteur Korea, Seongnam 13488, Republic of Korea
| | - Sunkyung Lee
- Drug Information Platform Center, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea; Korea University of Science and Technology, Daejeon 34114, Republic of Korea.
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27
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Development of Next Generation Streptococcus pneumoniae Vaccines Conferring Broad Protection. Vaccines (Basel) 2020; 8:vaccines8010132. [PMID: 32192117 PMCID: PMC7157650 DOI: 10.3390/vaccines8010132] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 02/22/2020] [Accepted: 02/29/2020] [Indexed: 02/06/2023] Open
Abstract
Streptococcus pneumoniae is a major pathogen causing pneumonia with over 2 million deaths annually, especially in young children and the elderly. To date, at least 98 different pneumococcal capsular serotypes have been identified. Currently, the vaccines for prevention of S. pneumoniae infections are the 23-valent pneumococcal polysaccharide-based vaccine (PPV23) and the pneumococcal conjugate vaccines (PCV10 and PCV13). These vaccines only cover some pneumococcal serotypes and are unable to protect against non-vaccine serotypes and unencapsulated S. pneumoniae. This has led to a rapid increase in antibiotic-resistant non-vaccine serotypes. Hence, there is an urgent need to develop new, effective, and affordable pneumococcal vaccines, which could cover a wide range of serotypes. This review discusses the new approaches to develop effective vaccines with broad serotype coverage as well as recent development of promising pneumococcal vaccines in clinical trials. New vaccine candidates are the inactivated whole-cell vaccine strain (Δpep27ΔcomD mutant) constructed by mutations of specific genes and several protein-based S. pneumoniae vaccines using conserved pneumococcal antigens, such as lipoprotein and surface-exposed protein (PspA). Among the vaccines in Phase 3 clinical trials are the pneumococcal conjugate vaccines, PCV-15 (V114) and 20vPnC. The inactivated whole-cell and several protein-based vaccines are either in Phase 1 or 2 trials. Furthermore, the recent progress of nanoparticles that play important roles as delivery systems and adjuvants to improve the performance, as well as the immunogenicity of the nanovaccines, are reviewed.
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28
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Sempere J, de Miguel S, González-Camacho F, Yuste J, Domenech M. Clinical Relevance and Molecular Pathogenesis of the Emerging Serotypes 22F and 33F of Streptococcus pneumoniae in Spain. Front Microbiol 2020; 11:309. [PMID: 32174903 PMCID: PMC7056674 DOI: 10.3389/fmicb.2020.00309] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 02/12/2020] [Indexed: 12/21/2022] Open
Abstract
Streptococcus pneumoniae is the main bacterial cause of respiratory infections in children and the elderly worldwide. Serotype replacement is a frequent phenomenon after the introduction of conjugated vaccines, with emerging serotypes 22F and 33F as frequent non-PCV13 serotypes in children and adults in North America and other countries. Characterization of mechanisms involved in evasion of the host immune response by these serotypes is of great importance in public health because they are included in the future conjugated vaccines PCV15 and PCV20. One of the main strategies of S. pneumoniae to persistently colonize and causes infection is biofilm formation. In this study, we have evaluated the influence of capsule polysaccharide in biofilm formation and immune evasion by using clinical isolates from different sources and isogenic strains with capsules from prevalent serotypes. Since the introduction of PCV13 in Spain in the year 2010, isolates of serotypes 22F and 33F are rising among risk populations. The predominant circulating genotypes are ST43322F and ST71733F, being CC433 in 22F and CC717 in 33F the main clonal complexes in Spain. The use of clinical isolates of different origin, demonstrated that pediatric isolates of serotypes 22F and 33F formed better biofilms than adult isolates and this was statistically significant. This phenotype was greater in clinical isolates from blood origin compared to those from cerebrospinal fluid, pleural fluid and otitis. Opsonophagocytosis assays showed that serotype 22F and 33F were recognized by the PSGL-1 receptor on leukocytes, although serotype 22F, was more resistant than serotype 33F to phagocytosis killing and more lethal in a mouse sepsis model. Overall, the emergence of additional PCV15 serotypes, especially 22F, could be associated to an enhanced ability to divert the host immune response that markedly increased in a biofilm state. Our findings demonstrate that pediatric isolates of 22F and 33F, that form better biofilm than isolates from adults, could have an advantage to colonize the nasopharynx of children and therefore, be important in carriage and subsequent dissemination to the elderly. The increased ability of serotype 22F to avoid the host immune response, might explain the emergence of this serotype in the last years.
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Affiliation(s)
- Julio Sempere
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain
| | - Sara de Miguel
- Servicio de Epidemiología de la Comunidad de Madrid, Dirección General de Salud Pública, Madrid, Spain
| | | | - José Yuste
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
| | - Mirian Domenech
- Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain
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29
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Garmpi A, Damaskos C, Garmpis N, Patsouras A, Savvanis S, Gravvanis N, Diamantis E. Pneumococcal Vaccination Strategies Among HIV-infected Adult Patients: A Review of the Literature. In Vivo 2020; 33:1425-1430. [PMID: 31471388 DOI: 10.21873/invivo.11620] [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: 06/11/2019] [Revised: 07/21/2019] [Accepted: 07/22/2019] [Indexed: 11/10/2022]
Abstract
BACKGROUND/AIM Streptococcus pneumoniae is the leading cause of bacterial pneumonia and an important cause of invasive disease. Despite the antiretroviral therapies, adults infected with human immunodeficiency virus (HIV) are at particular risk for invasive pneumococcal disease (IPD). The purpose of this study was to report the efficacy of the strategies currently being used in pneumococcal vaccination for HIV-infected adults. MATERIALS AND METHODS A literature search was performed through electronic databases, for original articles in English, from years 2000 to 2019. Clinical trials controlled or randomized, and cohort studies were included. RESULTS While 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for immunocompromised patients, it has been reported that it is less suitable for HIV-infected patients. Recent guidelines have added pneumococcal conjugate vaccine (PCV) to the list of recommended vaccines. CONCLUSION Further studies are needed to determine the optimal vaccines and intervals for subsequent revaccinations during the lifetime.
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Affiliation(s)
- Anna Garmpi
- Internal Medicine Department, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Christos Damaskos
- Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Nikolaos Garmpis
- Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Spyridon Savvanis
- Department of Internal Medicine, Elpis General Hospital, Athens, Greece
| | | | - Evangelos Diamantis
- Department of Endocrinology and Diabetes Center, G. Gennimatas General Hospital, Athens, Greece
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30
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Dhar R, Ghoshal AG, Guleria R, Sharma S, Kulkarni T, Swarnakar R, Samaria JK, Chaudhary S, Gaur SN, Christopher DJ, Singh V, Abraham G, Sarkar A, Mukhopadhyay A, Panda J, Swaminathan S, Nene A, Krishnan S, Shahi PK, Sarangdhar N, Mishra N, Chowdury SR, Halder I, Katiyar SK, Jain VK, Chawla R, Koul PA. Clinical practice guidelines 2019: Indian consensus-based recommendations on pneumococcal vaccination for adults. Lung India 2020; 37:S19-S29. [PMID: 32830790 PMCID: PMC7703813 DOI: 10.4103/lungindia.lungindia_272_20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Similar to the global scenario, pneumococcal diseases are a significant health concern in India. Pneumococcal diseases occur frequently among adults and are largely preventable through vaccines. Globally, several guidelines and recommendations are available for pneumococcal vaccination in adults. However, owing to wide variations in the disease burden, regulatory landscape, and health-care system in India, such global guidelines cannot be unconditionally implemented throughout the country. To address these gaps, the Indian Chest Society and National College of Chest Physicians of India jointly conducted an expert meeting in January 2019. The aim of the discussion was to lay down specific evidence-based recommendations on adult pneumococcal vaccination for the country, with a view to further ameliorate the disease burden in the country. This article presents an overview of the closed-door discussion by the expert members on clinical practice guidelines to be followed for adult pneumococcal vaccination in India.
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Affiliation(s)
- Raja Dhar
- Department of Pulmonology, Fortis Hospital, Kolkata, West Bengal, India
| | - Aloke Gopal Ghoshal
- Department of Pulmonary Medicine, National Allergy Asthma Bronchitis Institute, Kolkata, West Bengal, India
| | - Randeep Guleria
- Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
| | - Shubham Sharma
- Department of Pulmonology and Critical Care Medicine, Fortis Hospital, Kolkata, West Bengal, India
| | - Tarang Kulkarni
- Department of Pulmonology and Critical Care Medicine, Fortis Hospital, Kolkata, West Bengal, India
| | - Rajesh Swarnakar
- Department of Respiratory, Critical Care and Sleep Medicine, Getwell Hospital and Research Institute, Nagpur, Maharashtra, India
| | - J K Samaria
- Department of TB and Chest Diseases, Centre for Research and Treatment of Allergy, Asthma and Bronchitis, Varanasi, Uttar Pradesh, India
| | - Sudhir Chaudhary
- Department of Pulmonology, Kulwanti Hospitals and Research Center, Kanpur, Uttar Pradesh, India
| | - S N Gaur
- Department of Respiratory Medicine and Tuberculosis, School of Medical Sciences and Research, Greater Noida, Uttar Pradesh, India
| | - D J Christopher
- Department of Pulmonary Medicine, Christian Medical College, Vellore, Tamil Nadu, India
| | - Virendra Singh
- Department of Pulmonary Medicine, Asthma Bhawan, Shastri Nagar, Jaipur, Rajasthan, India
| | - Georgi Abraham
- Department of Nephrology, Madras Medical Mission, Chennai, Tamil Nadu, India
| | - Anirban Sarkar
- Department of Pulmonology, Zenith Superspeciality Hospital, Kolkata, West Bengal, India
| | - Ansuman Mukhopadhyay
- Department of Pulmonology, National Allergy Asthma Bronchitis Institute, Kolkata, West Bengal, India
| | - Jayant Panda
- Department of Medicine, SCB Medical College, Cuttack, Odisha, India
| | | | - Amita Nene
- Department of Chest Medicine, Bombay Hospital, Mumbai, Maharashtra, India
| | - Shyam Krishnan
- Department of Chest Medicine, Apollo Hospital, Bengaluru, Karnataka, India
| | - Praveen Kumar Shahi
- Department of Pulmonology and Critical Care Medicine, Fortis Hospital, Kolkata, West Bengal, India
| | - Nikhil Sarangdhar
- Department of Pulmonary Medicine, Lung Clinica, Andheri West Mumbai, Maharashtra, India
| | - Narayan Mishra
- Department of Pulmonary Medicine, MKCG Medical College, Berhampur, Odisha, India
| | | | - Indranil Halder
- Department of Pulmonary Medicine, College Of Medicine & JNM Hospital, Kalyani, Nadia, Uttar Pradesh, India
| | - S K Katiyar
- Chest Care Center, Kanpur, Uttar Pradesh, India
| | - V K Jain
- Department of Respiratory Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India
| | - Rakesh Chawla
- Dr Rakesh Chawla's Chest, Asthma Allergy and Sleep Clinic, Delhi, India
| | - Parvaiz A Koul
- Department of Internal and Pulmonary Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
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Albrich WC, Rassouli F, Waldeck F, Berger C, Baty F. Influence of Older Age and Other Risk Factors on Pneumonia Hospitalization in Switzerland in the Pneumococcal Vaccine Era. Front Med (Lausanne) 2019; 6:286. [PMID: 31867337 PMCID: PMC6906144 DOI: 10.3389/fmed.2019.00286] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 11/21/2019] [Indexed: 01/04/2023] Open
Abstract
Background: Pneumococcal pneumonia is a disease of the extremes of age. However, as other traditional risk factors for pneumococcal pneumonia also increase with older age, it is unclear if older age itself should be an indication for pneumococcal vaccination. Therefore, we assessed the effect of age on risk for hospitalization for pneumonia and for pneumococcal pneumonia. Methods: Using a national hospitalization dataset, all patients ≥16 years hospitalized in a Swiss hospital with a diagnosis of pneumonia or pneumococcal pneumonia between 2002 and 2015 were included. Multivariable logistic regression analysis was used to test the association between age (≥50 or ≥65 years) and hospitalization for pneumonia or pneumococcal pneumonia after adjusting for pneumococcal vaccine indications. Similar analyses were performed for effect of age on length of stay (LOS) and mortality. Results: Among a total of 17,619,016 hospitalizations a diagnosis of pneumonia was present in 421,760 (2.4%) and a diagnosis of pneumococcal pneumonia in 21,610 (0.12%). Age ≥50 years (OR: 3.52 and 2.12, respectively; p for both <0.001) and age ≥65 years (OR: 2.98 and 1.80, respectively; p for both <0.001) as well as most Swiss pneumococcal vaccine indications were independent predictors of hospitalization with a pneumonia and pneumococcal pneumonia diagnosis, respectively. Older age with both age cut-offs were associated with increased LOS (≥50 years: aRR: 1.19 and 1.24, respectively; age ≥65 years: aRR: 1.60 and 1.20, respectively; p < 0.001 for all) and mortality (≥50 years: aOR: 4.73 and 2.84, respectively; age ≥65 years: aOR: 2.38 and 2.69, respectively, p < 0.001 for all) in patients with a pneumonia and pneumococcal pneumonia diagnosis, respectively. The effects of pneumococcal vaccine indications decreased with older age. The incidences of hospitalizations with a pneumonia diagnosis and a pneumococcal pneumonia diagnosis increased significantly from the pre-vaccine era to the PCV7 era and the PCV13 era (p for trend for both analyses <0.001). Conclusion: This study confirms the Swiss indications for pneumococcal vaccination as independent risk factors for pneumonia hospitalizations. Older age itself should be considered as an additional vaccine indication. Pneumonia and pneumococcal pneumonia in adults have increased despite pneumococcal vaccination in children.
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Affiliation(s)
- Werner C. Albrich
- Division Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Frank Rassouli
- Department of Pulmonary and Sleep Medicine, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Frederike Waldeck
- Division Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Christoph Berger
- Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital Zürich, Zurich, Switzerland
| | - Florent Baty
- Department of Pulmonary and Sleep Medicine, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
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El-Bardissy AHE, Al‐Adawi RM, Shible AA, Albu‐Mahmood Z, Elgaily DE, Abdelaziz H. Evaluating the effectiveness of pneumococcal vaccines against hospitalization and intensive care unit admission in adults. JOURNAL OF PHARMACEUTICAL HEALTH SERVICES RESEARCH 2019. [DOI: 10.1111/jphs.12321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
| | | | - Ahmed Atef Shible
- Pharmacy Department Hamad General Hospital Hamad Medical Corporation Doha Qatar
| | - Zainab Albu‐Mahmood
- Pharmacy Department Hamad General Hospital Hamad Medical Corporation Doha Qatar
| | | | - Hani Abdelaziz
- Pharmacy Department Al Wakra Hospital Hamad Medical Corporation Doha Qatar
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Autran B. [Alterations in responses to vaccines in older people]. Rev Mal Respir 2019; 36:1047-1056. [PMID: 31522947 DOI: 10.1016/j.rmr.2019.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 07/08/2019] [Indexed: 11/28/2022]
Abstract
The aging population raises a number of public health issues including a need to address the severity and frequency of infections observed in older people. Vaccines play an important role in prevention. However, immunosenescence alters the intensity and quality of vaccine responses, thus limiting the impact of recommendations directed after 65 years for vaccination against flu, pneumococci, pertussis, tetanus and zoster. Immunosenescence, aggravated by co-morbidities, varies with age, becoming apparent after 60-65 years and more profound after 85 years. All stages of vaccine responses are affected by immunosenescence, from the innate immunity required to activate these responses to the induction of protective antibody responses and immune memory. Nevertheless, the capacity to develop new responses to primary vaccination is more affected than the ability to respond to recalls, although this is also impaired. Responses to vaccines are differentially altered depending on vaccine and age. Influenza vaccines are modestly immunogenic and several meta-analyses agree an estimate for efficacy of about 50% against virologically-proven flu and 40% against flu-related deaths. The anti-pneumococcal 23-valent non-conjugated vaccine does not induce memory while the 13-valent conjugated one does, but their efficacy are likely to be similar between 70 to 52% before 75 years. A sequential vaccination program with the 13-valent primo-vaccination followed by the 23-valent, recommended in immune-suppressed patients, is currently being studied in France. The waning of immunity to pertussis makes recalls necessary in the elderly who develop good antibody responses. Several research avenues are currently being pursued to try improve the degree of protection conferred by these vaccines in elderly.
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Affiliation(s)
- B Autran
- Sorbonne-université, 75005 Paris, France; UMR-S Inserm/UPMC 1135), CIMI-Paris (centre de recherches immunité maladies infectieuses), 83, boulevard de l'Hôpital, 75013 Paris, France.
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Treskova M, Scholz SM, Kuhlmann A. Cost Effectiveness of Elderly Pneumococcal Vaccination in Presence of Higher-Valent Pneumococcal Conjugate Childhood Vaccination: Systematic Literature Review with Focus on Methods and Assumptions. PHARMACOECONOMICS 2019; 37:1093-1127. [PMID: 31025189 DOI: 10.1007/s40273-019-00805-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
BACKGROUND Previous systematic reviews concluded that pneumococcal vaccination in the elderly was cost effective. However, recently published economic evaluations state that it may not be cost effective when children are vaccinated with higher-valent pneumococcal conjugate vaccines. The literature suggests that the outcomes of vaccination in the elderly are strongly influenced by the vaccine effectiveness (VE) against the vaccine-type pneumococcal diseases (PD) and the impact of childhood vaccination on the vaccine-type PD incidence in the elderly, but the extent remains unclear. METHODS We conducted a systematic literature search of cost-effectiveness studies on vaccination in the elderly in the PubMed database starting from 2006. We included studies that consider the presence of a childhood vaccination with pneumococcal conjugate vaccine (PCV) 10 and PCV13. We focus on methods and assumptions used in modeling VE and epidemiology of PD over time. RESULTS Twenty-eight economic evaluations underwent full-text review and data extraction. Thirteen were selected for quality assessment. The studies with a higher quality score provide evidence that vaccinating the elderly with PCV13 is not cost effective, when an ongoing rapid decline in the incidence of PCV13-type PD is modeled. A moderate persistence of PCV13 serotypes, in particular due to PCV10 childhood vaccination, makes vaccination of the elderly with PCV13 more attractive. There is no agreement that combining PCV13 with polysaccharide vaccine PPSV23 is cost effective. PPSV23 is attractive when it is effective against non-invasive PD. CONCLUSION Methodological approaches and assumptions in modeling VE and the indirect effects of childhood vaccination have a major impact on outcomes of decision-analytic models and cost-effectiveness estimates. Considering recently observed trends in the epidemiology of pneumococcal serotypes, there is currently inconclusive evidence regarding the cost effectiveness of pneumococcal vaccination of the elderly due to lack of studies that model key serotypes such as serotype 3 separately from other groups of serotypes.
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Affiliation(s)
- Marina Treskova
- Center for Health Economics Research Hannover (CHERH), Leibniz Universität Hannover, Otto-Brenner-Str.7, 30159, Hannover, Germany.
| | - Stefan M Scholz
- Center for Health Economics Research Hannover (CHERH), Leibniz Universität Hannover, Otto-Brenner-Str.7, 30159, Hannover, Germany
- Department of Health Economics and Health Management, School of Public Health, Bielefeld University, Bielefeld, Germany
| | - Alexander Kuhlmann
- Center for Health Economics Research Hannover (CHERH), Leibniz Universität Hannover, Otto-Brenner-Str.7, 30159, Hannover, Germany
- Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany
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Gonçalves VM, Kaneko K, Solórzano C, MacLoughlin R, Saleem I, Miyaji EN. Progress in mucosal immunization for protection against pneumococcal pneumonia. Expert Rev Vaccines 2019; 18:781-792. [PMID: 31305196 DOI: 10.1080/14760584.2019.1643719] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Introduction: Lower respiratory tract infections are the fourth cause of death worldwide and pneumococcus is the leading cause of pneumonia. Nonetheless, existing pneumococcal vaccines are less effective against pneumonia than invasive diseases and serotype replacement is a major concern. Protein antigens could induce serotype-independent protection, and mucosal immunization could offer local and systemic immune responses and induce protection against pneumococcal colonization and lung infection. Areas covered: Immunity induced in the experimental human pneumococcal carriage model, approaches to address the physiological barriers to mucosal immunization and improve delivery of the vaccine antigens, different strategies already tested for pneumococcal mucosal vaccination, including live recombinant bacteria, nanoparticles, bacterium-like particles, and nanogels as well as, nasal, pulmonary, sublingual and oral routes of vaccination. Expert opinion: The most promising delivery systems are based on nanoparticles, bacterial-like particles or nanogels, which possess greater immunogenicity than the antigen alone and are considered safer than approaches based on living cells or toxoids. These particles can protect the antigen from degradation, eliminating the refrigeration need during storage and allowing the manufacture of dry powder formulations. They can also increase antigen uptake, control release of antigen and trigger innate immune responses.
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Affiliation(s)
| | - Kan Kaneko
- b School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University James Parsons Building , Liverpool , UK
| | - Carla Solórzano
- c Department of Clinical Sciences, Liverpool School of Tropical Medicine , Liverpool , UK
| | - Ronan MacLoughlin
- d Science Department and Clinical Department, Aerogen Ltd., IDA Business Park , Galway , Ireland
| | - Imran Saleem
- b School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University James Parsons Building , Liverpool , UK
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van Werkhoven CH, Huijts SM. Vaccines to Prevent Pneumococcal Community-Acquired Pneumonia. Clin Chest Med 2019; 39:733-752. [PMID: 30390745 DOI: 10.1016/j.ccm.2018.07.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Streptococcus pneumoniae is the most frequent pathogen in community-acquired pneumonia and also causes invasive diseases like bacteremia and meningitis. Young children and elderly are especially at risk for pneumococcal diseases and are, therefore, eligible for pneumococcal vaccination in most countries. This reviews provides an overview of the current epidemiology of pneumococcal infections, history and evidence of available pneumococcal polysaccharide and conjugate vaccines, and current recommendations.
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Affiliation(s)
- Cornelis H van Werkhoven
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO-Box 85500, Utrecht 3508 GA, The Netherlands.
| | - Susanne M Huijts
- Department of Respiratory Medicine, University Medical Center Utrecht, PO-Box 85500, Utrecht 3508 GA, The Netherlands
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Park SB, Kim HJ, Cheong HJ. Environmental factors which can affect the burden of pneumococcal disease and the immune response to pneumococcal vaccines: the need for more precisely delineated vaccine recommendations. Expert Rev Vaccines 2019; 18:587-596. [PMID: 30998430 DOI: 10.1080/14760584.2019.1607303] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Introduction: Precision medicine describes the customization of healthcare tailored to the individual patient. Generally, vaccines are considered as public health tools rather than from the individual patient perspective. However, adult vaccination programs in particular should consider many different factors, at the individual level and also from societal, cultural and country-specific perspectives. Currently, most immunization programs, including those for pneumococcal vaccines, have only been adopted on the basis of age or medical risk. Areas covered: Based on a broad literature search, this review addresses possible environmental factors which can affect the burden of pneumococcal disease and the immune response to pneumococcal vaccines. Expert opinion: Factors which influence the incidence of pneumococcal disease and the reaction against pneumococcal vaccination, including personal conditions, geographic/ethnic factors and social risks, are diverse. To maximize the effects of pneumococcal vaccination, not only for public health but also to induce optimal effects at the individual level, vaccines need to be verified under diverse situations and with collaboration among relevant medical societies, governments, and the pharmaceutical industry. Whereas vaccines are generally considered only from the public health perspective, flexible, comprehensive and tailored pneumococcal immunization programs, with appropriate policy support, can generate a greater positive impact on public health.
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Affiliation(s)
- Seong-Beom Park
- a Pfizer Pharmaceuticals Korea Ltd ., Seoul , Republic of Korea
| | - Hyun-Jin Kim
- a Pfizer Pharmaceuticals Korea Ltd ., Seoul , Republic of Korea
| | - Hee-Jin Cheong
- b Division of Infectious Diseases, Department of Internal Medicine , Guro Hospital, Korea University College of Medicine , Seoul , Republic of Korea
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Wiese AD, Griffin MR, Grijalva CG. Impact of pneumococcal conjugate vaccines on hospitalizations for pneumonia in the United States. Expert Rev Vaccines 2019; 18:327-341. [PMID: 30759352 PMCID: PMC6443450 DOI: 10.1080/14760584.2019.1582337] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Accepted: 02/11/2019] [Indexed: 01/05/2023]
Abstract
INTRODUCTION Pneumonia is one of the leading causes of morbidity and mortality among children and older adults. Pneumococcal conjugate vaccines (PCVs) were introduced into the US routine infant vaccination schedule leading to substantial reductions of invasive pneumococcal diseases (IPD). PCV introduction also led to reductions in all-cause pneumonia among US children, though the indirect impact of PCVs on pneumonia in adults is difficult to quantify, especially due to the recent US recommendation for direct PCV use in older adults. Areas covered: We described the existing evidence for both the direct and indirect impact of PCVs on pneumonia among children and adults in the US since PCV introduction. Expert commentary: The introduction of PCVs into the US routine infant vaccination schedule led to important reductions in the burden of IPD and non-invasive pneumonia among vaccinated and unvaccinated populations. The impact of direct vaccination of older adults in the US since 2014, though difficult to quantify, is currently being evaluated. As pneumonia remains one of the leading causes of morbidity and mortality in the US, future evaluations of the direct and indirect effects of current and expanded valency PCVs in the US population are needed.
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Affiliation(s)
- Andrew D. Wiese
- Department of Health Policy, Vanderbilt University, Nashville, Tennessee, USA
| | - Marie R. Griffin
- Department of Health Policy, Vanderbilt University, Nashville, Tennessee, USA
- Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA
- The Mid-South Geriatric Research Education and Clinical Center, VA Tennessee Valley Health Care System, Nashville, Tennessee, USA
| | - Carlos G. Grijalva
- Department of Health Policy, Vanderbilt University, Nashville, Tennessee, USA
- Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA
- The Mid-South Geriatric Research Education and Clinical Center, VA Tennessee Valley Health Care System, Nashville, Tennessee, USA
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Marra F, Vadlamudi NK. Efficacy and Safety of the Pneumococcal Conjugate-13 Valent Vaccine in Adults. Aging Dis 2019; 10:404-418. [PMID: 31011485 PMCID: PMC6457056 DOI: 10.14336/ad.2018.0512] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Accepted: 05/04/2018] [Indexed: 12/29/2022] Open
Abstract
Invasive pneumococcal disease and pneumococcal pneumonia cause substantial morbidity and mortality in the elderly. This review focuses on the immunogenicity, safety, efficacy and effectiveness data on the use of the 13-valent conjugate pneumococcal vaccine (PCV13) in adults. A MEDLINE literature search was performed from January 1946 to December 2017. Additional references were identified from a review of literature citations. All English-language randomized trials, observational studies and meta-analyses assessing the immunogenicity, efficacy, effectiveness and safety of PCV13 in adults were evaluated. Six randomized controlled studies evaluated immunogenicity and safety of PCV13 in adults and showed that the conjugated vaccine elicited a greater immune response to the majority of the 13 serotypes compared to the 23-valent polysaccharide pneumococcal vaccine (PPV23). Administering PCV13 prior to PPV23 elicits greater immune responses and multiple doses of PCV13 demonstrated modest advantage. PCV13 titers declined after a year but remained above baseline. A randomized clinical trial (CAPiTA) showed that PCV13 was effective in preventing community-acquired pneumonia (CAP) and vaccine-type invasive pneumococcal disease, but not any cause pneumonia. Safety data shows PCV13 elicits minor local reactions, such as pain at the injection site. Major side effects that were commonly reported included muscle fatigue and headache. Both local and systemic adverse events were comparable to PPV23. While PCV13 has a well-established immunogenicity and safety profile in adults, there is sparse data on sequential or multiple dosing, efficacy and effectiveness in adults. As there are few countries who have adopted PCV13 for routine adult immunization, there is a need to evaluate the effectiveness of PCV13 in a real-world setting.
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Affiliation(s)
- Fawziah Marra
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada
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Kislaya I, Rodrigues AP, Sousa-Uva M, Gómez V, Gonçalves P, Froes F, Nunes B. Indirect effect of 7-valent and 13-valent pneumococcal conjugated vaccines on pneumococcal pneumonia hospitalizations in elderly. PLoS One 2019; 14:e0209428. [PMID: 30650091 PMCID: PMC6334925 DOI: 10.1371/journal.pone.0209428] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2018] [Accepted: 12/05/2018] [Indexed: 01/15/2023] Open
Abstract
Background Pneumonia is one of the leading causes of mortality and has a high burden in morbidity. In Portugal, 7-valent pneumococcal conjugated vaccine (PCV) was used since 2001 and PCV10/13 since 2009, being the last introduced into the National Immunization Program in 2015. Methods We conducted an ecological study to evaluate the impact of PCV7 and PCV13 on pneumococcal pneumonia (PP) hospitalizations in adults aged 65 years or more in Portugal. National hospital discharge registry data from 1998/99 to 2015/16 were used, and PP hospitalization was defined as any hospitalization coded in primary diagnosis as 481 (ICD-9-CM) or J18 (ICD-10-CM). Poisson regression models adjusted for seasonality, influenza-like illness and allowing for overdispersion was used to estimate annual average change of PP hospitalization rate. To assess PP hospitalization trends before and after PCV7 and PCV13 introduction interrupted time series analysis was performed. Results In 1998/99 PP hospitalization rate was 7.0 per 10,000 inhabitants, varying between 3.2 (females, 65–74 years) to 20.7 (males, +85 years), and annually increasing by 16% during the pre-PCV7 period. Statistically significant reduction of 14% per year in PP hospitalization rate was observed after PCV7 introduction. Between 2004/05 and 2009/10 PP hospitalization rate decreased annually by 4% and after PCV13 introduction by 11% per year. In 2015/16 we found an overall reduction of 2.9 (CI 95%: 2.7; 3.1) PP hospitalizations per 10,000 inhabitants (598 hospitalizations) attributable to PCV13, varying from 2.2 (CI 95%: 1.3; 3.1) (female, 65–74 years) to 5.6 (CI 95%: 3.8; 7.5) (female, +85 years). Conclusions Our results suggest that introduction of both PCV7 and PCV13 vaccines resulted in the reduction of PP hospitalizations rates among older adults.
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Affiliation(s)
- Irina Kislaya
- Departamento de Epidemiologia, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal
- Centro de Investigação em Saúde Pública, Escola Nacional de Saúde Pública, Universidade Nova de Lisboa, Lisboa, Portugal
| | - Ana Paula Rodrigues
- Departamento de Epidemiologia, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal
- * E-mail:
| | - Mafalda Sousa-Uva
- Departamento de Epidemiologia, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal
- Centro de Investigação em Saúde Pública, Escola Nacional de Saúde Pública, Universidade Nova de Lisboa, Lisboa, Portugal
| | - Verónica Gómez
- Departamento de Epidemiologia, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal
| | - Paulo Gonçalves
- Departamento de Doenças Infecciosas, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal
| | - Filipe Froes
- Thorax Department, Centro Hospitalar Lisboa Norte, Lisboa, Portugal
| | - Baltazar Nunes
- Departamento de Epidemiologia, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal
- Centro de Investigação em Saúde Pública, Escola Nacional de Saúde Pública, Universidade Nova de Lisboa, Lisboa, Portugal
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Abstract
Invasive infections caused by Streptococcus pneumoniae, such as pneumonia, meningitis, and bacteremia, are a major cause of morbidity and mortality in young children and older adults worldwide. The introduction of pneumococcal conjugate vaccines into national childhood immunization programs has led to large and sustained reductions in the incidence of invasive pneumococcal disease across all age groups. Here we describe the epidemiology and biostatistics of pneumococcal disease as well as the impact of vaccination on the burden of pneumococcal disease globally.
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Affiliation(s)
- Godwin Oligbu
- Paediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St. George's, University of London, London, UK.
- Immunisation and Countermeasures Division, National Infection Service, Public Health England, London, UK.
| | - Norman K Fry
- Immunisation and Countermeasures Division, National Infection Service, Public Health England, London, UK
- Respiratory and Vaccine Preventable Bacterial Reference Unit (RVPBRU), National Infection Service Laboratories, Public health England, London, UK
| | - Shamez N Ladhani
- Paediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St. George's, University of London, London, UK
- Immunisation and Countermeasures Division, National Infection Service, Public Health England, London, UK
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Abstract
Thirteen-valent pneumococcal conjugate vaccine (PCV13) was licensed in adults to address the unmet medical need of vaccine-type community acquired pneumonia (CAP) and the limitations of previous plain-polysaccharide vaccines. Since then, some have questioned the utility of adult PCV13 use, arguing that: i) high PCV13 uptake in young children would provide indirect effects that, by themselves, would sufficiently protect unvaccinated adults and ii) no data describing the real-world effectiveness of PCV13 use in adults, especially with immunocompromising conditions, exist. Even in countries like the United States where PCV13 has been routinely recommended for all adults aged ≥ 65 years, the recommendation is contingent on a re-evaluation to determine if continued use is needed in the context of a mature PCV13 pediatric immunization program. Emerging evidence, however, suggests that i) a meaningful burden of PCV13-type pneumococcal pneumonia still persists in adults at increased risk for pneumococcal disease, despite indirect effects from long-standing pediatric PCV13 use, ii) adult PCV13 use is effective and has reduced pneumococcal CAP, even in the elderly and those with chronic medical or immunocompromising conditions – and disease could come back if PCV13 were removed, and iii) ethical and pragmatic vaccine policy considerations support continued adult PCV13 use in countries that have already introduced the vaccine (eg, disparities in adult PCV13 uptake, confusion stemming from removing a previously-recommended vaccine for a non-safety-related concern, and the reality that next-generation PCVs are only a few years away). Together, these findings suggest that continued PCV13 vaccination in adults is needed to control vaccine-type CAP.
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Affiliation(s)
| | | | | | - Luis Jodar
- a Pfizer Vaccines , Collegeville , PA , USA
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Cost-Utility Study of PCV13 Versus PPSV23 in Adults in Chile. Value Health Reg Issues 2018; 17:194-201. [PMID: 30447540 DOI: 10.1016/j.vhri.2018.09.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Revised: 09/11/2018] [Accepted: 09/17/2018] [Indexed: 11/21/2022]
Abstract
INTRODUCTION Pneumococcal infections are a public health problem in older adults. In Chile there are two vaccines at this time, PPSV23 and PCV13. The first has lower immunogenicity and effectiveness in preventing pneumococcal pneumonia and a lower cost than PCV13. OBJECTIVE To determine the cost-effectiveness of PCV13 versus PPSV23 in adults 18 years old and over in the Chilean Health System. MATERIAL AND METHOD A cost-utility study was performed using the Markov model (population data for a time horizon of 10 years). Utilities and epidemiological data were obtained from the literature and costs from the Chilean Public sector. Vaccine's costs and quality-adjusted life years (QALYs) were determined and compared. RESULTS PCV13 vaccination program in adults (≥18 years), generated savings of $42,195 USD and an increase of 6,820 QALYs, avoiding 107 cases of bacteremia, 13 meningitis, 6,706 inpatient pneumonia, 4,509 outpatient pneumonia and 1,189 deaths compared to PPSV23 without variation on sensitivity analysis on high impact variables. For the subgroup of patients over 65 years old PCV13 generates savings of $ 32,105.94USD and produces 5,430 QALYs more compared to PPSV23. CONCLUSION PCV13 is dominant. A PCV13 vaccination program saves costs to the public system, reduces mortality and morbidity; these results are robust.
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Geretti AM, Brook G, Cameron C, Chadwick D, French N, Heyderman R, Ho A, Hunter M, Ladhani S, Lawton M, MacMahon E, McSorley J, Pozniak A, Rodger A. British HIV Association Guidelines on the Use of Vaccines in HIV-Positive Adults 2015. HIV Med 2018; 17 Suppl 3:s2-s81. [PMID: 27568789 DOI: 10.1111/hiv.12424] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Anna Maria Geretti
- Institute of Infection and Global Health, University of Liverpool, Liverpool, UK
| | | | | | | | | | | | | | | | | | - Mark Lawton
- Royal Liverpool University Hospital, Liverpool, UK
| | - Eithne MacMahon
- Guy's & St Thomas' NHS Foundation Trust, London, UK.,King's College London, London, UK
| | | | - Anton Pozniak
- Chelsea and Westminster Hospital, NHS Foundation Trust, London, UK
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45
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Cools F, Torfs E, Vanhoutte B, de Macedo MB, Bonofiglio L, Mollerach M, Maes L, Caljon G, Delputte P, Cappoen D, Cos P. Streptococcus pneumoniae galU gene mutation has a direct effect on biofilm growth, adherence and phagocytosis in vitro and pathogenicity in vivo. Pathog Dis 2018; 76:5078866. [DOI: 10.1093/femspd/fty069] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Accepted: 08/22/2018] [Indexed: 11/13/2022] Open
Affiliation(s)
- F Cools
- University of Antwerp, Laboratory of Microbiology, Parasitology and Hygiene. Universiteitsplein 1, 2610 Wilrijk, Belgium
| | - E Torfs
- University of Antwerp, Laboratory of Microbiology, Parasitology and Hygiene. Universiteitsplein 1, 2610 Wilrijk, Belgium
| | - B Vanhoutte
- University of Antwerp, Laboratory of Microbiology, Parasitology and Hygiene. Universiteitsplein 1, 2610 Wilrijk, Belgium
| | - M Bidart de Macedo
- University of Antwerp, Laboratory of Microbiology, Parasitology and Hygiene. Universiteitsplein 1, 2610 Wilrijk, Belgium
| | - L Bonofiglio
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología, Biotecnología y Genética. Cátedra de Microbiología. Junín 956. Ciudad Autónoma de Buenos Aires, Argentina
| | - M Mollerach
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología, Biotecnología y Genética. Cátedra de Microbiología. Junín 956. Ciudad Autónoma de Buenos Aires, Argentina
| | - L Maes
- University of Antwerp, Laboratory of Microbiology, Parasitology and Hygiene. Universiteitsplein 1, 2610 Wilrijk, Belgium
| | - G Caljon
- University of Antwerp, Laboratory of Microbiology, Parasitology and Hygiene. Universiteitsplein 1, 2610 Wilrijk, Belgium
| | - P Delputte
- University of Antwerp, Laboratory of Microbiology, Parasitology and Hygiene. Universiteitsplein 1, 2610 Wilrijk, Belgium
| | - D Cappoen
- University of Antwerp, Laboratory of Microbiology, Parasitology and Hygiene. Universiteitsplein 1, 2610 Wilrijk, Belgium
| | - P Cos
- University of Antwerp, Laboratory of Microbiology, Parasitology and Hygiene. Universiteitsplein 1, 2610 Wilrijk, Belgium
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46
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Latifi-Navid H, Latifi-Navid S, Mostafaiy B, Jamalkandi SA, Ahmadi A. Pneumococcal Disease and the Effectiveness of the PPV23 Vaccine in Adults: A Two-Stage Bayesian Meta-Analysis of Observational and RCT Reports. Sci Rep 2018; 8:11051. [PMID: 30038423 PMCID: PMC6056566 DOI: 10.1038/s41598-018-29280-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Accepted: 07/10/2018] [Indexed: 12/12/2022] Open
Abstract
The efficacy of PPV-23 vaccine on outcomes of pneumococcal disease in adults still remains controversial due mainly to the lack of consistency between the results obtained from observational studies(OSs) and those obtained from randomized controlled trials(RCTs). As a consequence, the complexity in the structure of evidence available, in turn, generates a challenge for combining disparate pieces of evidence quantitatively. In this regard, we used a hierarchical Bayesian inference-based evidence synthesis of RCTs and observational data using a two-stage approach (in addition to a traditional random-effects meta-analysis) to examine the effectiveness of PPV-23 in adults. To this end, 21 studies were included involving 826109 adult participants. By a two-stage Bayesian meta-analysis, which was directly used for combining studies of different designs, the overall log OR (95% credible interval) for IPDs was -0.1048 (-0.3920,-0.0250), indicating a significant protective effect of the vaccination against IPDs. No significant effect of PPV-23 was found on all-cause pneumonia, pneumococcal pneumonia, and death from pneumonia, which confirmed the results obtained by a traditional method followed by stratified and sensitivity analyses. The estimated overall log OR (95% credible interval) was -0.0002 (-0.0241,0.0142), -0.0002 (-0.0110,0.0122), and -6.3912 × 10-5 (-0.0219,0.0131), respectively. The PPV-23 vaccine might be effective in preventing the most severe invasive forms of pneumococcal diseases, but not effective in preventing other clinical outcomes, in the adult population of 18 years and older.
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Affiliation(s)
- Hamid Latifi-Navid
- Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran.
- Biosciences and Biotechnology Research Center (BBRC), Faculty of Advanced Technologies, University of Mohaghegh Ardabili, Namin, Iran.
| | - Behdad Mostafaiy
- Department of Statistics, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Sadegh Azimzadeh Jamalkandi
- 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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47
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Yin M, Huang L, Zhang Y, Yu N, Xu X, Liang Y, Ni J. Effectiveness and safety of dual influenza and pneumococcal vaccination versus separate administration or no vaccination in older adults: a meta-analysis. Expert Rev Vaccines 2018; 17:653-663. [PMID: 29961353 DOI: 10.1080/14760584.2018.1495077] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Affiliation(s)
- Mingjuan Yin
- Department of Epidemiology and Biostatistics, Guangdong Medical University, Dongguan, China
| | - Lingfeng Huang
- Department of Epidemiology and Biostatistics, Guangdong Medical University, Dongguan, China
| | - Yan Zhang
- Department of Epidemiology and Biostatistics, Guangdong Medical University, Dongguan, China
| | - Na Yu
- Office of Research and Teaching, The Third Affiliated Hospital of GuangDong Medical University (LongJiang Hospital of Shunde District Fo Shan City), Fo Shan, China
| | - Xiaojia Xu
- Department of Epidemiology and Biostatistics, Guangdong Medical University, Dongguan, China
| | - Yaping Liang
- Department of Epidemiology and Biostatistics, Guangdong Medical University, Dongguan, China
| | - Jindong Ni
- Department of Epidemiology and Biostatistics, Guangdong Medical University, Dongguan, China
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48
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German EL, Al-Hakim B, Mitsi E, Pennington SH, Gritzfeld JF, Hyder-Wright AD, Banyard A, Gordon SB, Collins AM, Ferreira DM. Anti-protein immunoglobulin M responses to pneumococcus are not associated with aging. Pneumonia (Nathan) 2018; 10:5. [PMID: 29992080 PMCID: PMC5987460 DOI: 10.1186/s41479-018-0048-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Accepted: 05/10/2018] [Indexed: 11/16/2022] Open
Abstract
Background The incidence of community-acquired pneumonia and lower respiratory tract infection rises considerably in later life. Immunoglobulin M (IgM) antibody levels to pneumococcal capsular polysaccharide are known to decrease with age; however, whether levels of IgM antibody to pneumococcal proteins are subject to the same decline has not yet been investigated. Methods This study measured serum levels and binding capacity of IgM antibody specific to the pneumococcal surface protein A (PspA) and an unencapsulated pneumococcal strain in serum isolated from hospital patients aged < 60 and ≥ 60, with and without lower respiratory tract infection. A group of young healthy volunteers was used as a comparator to represent adults at very low risk of pneumococcal pneumonia. IgM serum antibody levels were measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry was performed to assess IgM binding capacity. Linear regression and one-way analysis of variance (ANOVA) tests were used to analyse the results. Results Levels and binding capacity of IgM antibody to PspA and the unencapsulated pneumococcal strain were unchanged with age. Conclusions These findings suggest that protein-based pneumococcal vaccines may provide protective immunity in the elderly. Trial registration The LRTI trial (LRTI and control groups) was approved by the National Health Service Research Ethics Committee in October 2013 (12/NW/0713). Recruitment opened in January 2013 and was completed in July 2013. Healthy volunteer samples were taken from the EHPC dose-ranging and reproducibility trial, approved by the same Research Ethics Committee in October 2011 (11/NW/0592). Recruitment for this study ran from October 2011 until December 2012. LRTI trial: (NCT01861184), EHPC dose-ranging and reproducibility trial: (ISRCTN85403723).
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Affiliation(s)
- Esther L German
- 1Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Bahij Al-Hakim
- 1Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK.,3Present address: Aintree University Hospital, Liverpool, UK
| | - Elena Mitsi
- 1Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Shaun H Pennington
- 1Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Jenna F Gritzfeld
- 1Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK.,Present address: Public Health England, Vaccine Evaluation Unit, Manchester, UK
| | | | - Antonia Banyard
- 1Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK.,5Present address: Cancer Research UK Manchester Institute, Manchester, UK
| | - Stephen B Gordon
- 1Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK.,6Present address: Malawi-Liverpool-Wellcome Trust, Blantyre, Malawi
| | - Andrea M Collins
- 1Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Daniela M Ferreira
- 1Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK
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49
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Choi MJ, Kang SO, Oh JJ, Park SB, Kim MJ, Cheong HJ. Cost-effectiveness analysis of 13-valent pneumococcal conjugate vaccine versus 23-valent pneumococcal polysaccharide vaccine in an adult population in South Korea. Hum Vaccin Immunother 2018; 14:1914-1922. [PMID: 29953307 PMCID: PMC6149703 DOI: 10.1080/21645515.2018.1456602] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 03/07/2018] [Accepted: 03/18/2018] [Indexed: 10/28/2022] Open
Abstract
In South Korea, the National Immunization Program offers a 23-valent pneumococcal polysaccharide vaccine (PPSV23) for the elderly; however, the 13-valent pneumococcal conjugate vaccine (PCV13) is not included, and vaccination is not offered to younger, at-risk populations. This study offers a comparative analysis of PCV13 and PPSV23 in Korea's adults, stratified by age and risk group. A Markov model with a lifetime horizon was developed from the healthcare perspective. Data sources included the Health Insurance Review & Assessment Service, Korea Centre for Disease Control & Prevention and Korean medical institutions. An expert panel tested data validity. The CAPiTA trial and Cochrane meta-analysis were used to obtain vaccine effectiveness data. Regardless of co-morbidity, when the sequential PCV13-PPSV23 strategy was compared to that using PPSV23-only, in elderly populations, the incremental cost-effectiveness ratio (ICER) was 3,300 USD per quality-adjusted life years (QALY). For the risk group aged ≥65 years, the ICER of the addition of PCV13 over the existing PPSV23-only strategy was 3,404 USD/QALY. However, on replacing PPSV23 with PCV13, for all elderly populations, an ICER of 1,421 USD/QALY resulted; for the risk group aged ≥65 years, the ICER was 1,736 USD/QALY. For the 18-64 year-old risk group, the sequential PCV13-PPSV23 strategy yielded an ICER of 3,629 USD/QALY over the PPSV23-only strategy, and 6,643 USD/QALY compared to no vaccination. Thus, the PCV13→PPSV23 combination strategy for elderly populations was found to be a cost-effective alternative to the current National Immunization Program regardless of co-morbidity. This finding was the same as that for younger, at-risk populations.
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Affiliation(s)
- Min-Joo Choi
- Division of Infectious Disease, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | | | | | | | - Min-Ja Kim
- Division of Infectious Disease, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Hee-Jin Cheong
- Division of Infectious Disease, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
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50
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Demczuk WHB, Martin I, Desai S, Griffith A, Caron-Poulin L, Lefebvre B, McGeer A, Tyrrell GJ, Zhanel GG, Gubbay J, Hoang L, Levett PN, Van Caeseele P, Raafat Gad R, Haldane D, Zahariadis G, German G, Daley Bernier J, Strudwick L, Mulvey MR. Serotype distribution of invasive Streptococcus pneumoniae in adults 65 years of age and over after the introduction of childhood 13-valent pneumococcal conjugate vaccination programs in Canada, 2010-2016. Vaccine 2018; 36:4701-4707. [PMID: 29937245 DOI: 10.1016/j.vaccine.2018.06.018] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Revised: 05/24/2018] [Accepted: 06/06/2018] [Indexed: 01/22/2023]
Abstract
The 13-valent conjugate vaccine (PCV13) was recommended for childhood immunization programs in 2010 in Canada and has decreased the incidence of invasive pneumococcal disease (IPD) in children and changed the epidemiology of IPD in adults. This study investigated the epidemiology of IPD in adults 65 years of age and older in Canada. A total of 7282 invasive S. pneumoniae isolated from adults ≥65 years old were serotyped from 2010 to 2016 and antimicrobial susceptibility was performed on 2527 isolates. Serotyping was performed by Quellung reaction using commercial antisera and antimicrobial susceptibilities were determined by broth microdilution. PCV7 serotypes decreased non-significantly from 2010 to 2016 from 9.1% (n = 96) to 6.7% (n = 72) while the additional six PCV13 serotypes declined significantly from 39.5% (n = 418) to 18.6% (n = 201) (p < 0.05). The 23-valent pneumococcal polysaccharide vaccine (PPV23) and non-vaccine (NVT) serotypes increased from 26.3% (n = 278) to 36.2% (n = 393) (p < 0.05), and from 25.1% (n = 266) to 38.4% (n = 416) (p < 0.05), respectively. There were no significant changes in antimicrobial resistance rates from 2011 to 2016: 24.1% of the IPD from adults ≥65 years were resistant to clarithromycin (n = 609), 10.0% to doxycycline (n = 254), 11.8% to penicillin (n = 299), 5.2% to cefuroxime (n = 131), 6.6% to clindamycin (n = 168), 6.0% to trimethoprim-sulfamethoxazole (n = 152), and 0.5% (n = 12) to ceftriaxone. Although overall incidence of IPD in adults ≥65 years has remained relatively constant from 2010 to 2016, childhood PCV13 vaccination programs have been successful in indirectly reducing IPD caused by PCV13 serotypes in adults through herd immunity effects.
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Affiliation(s)
- Walter H B Demczuk
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
| | - Irene Martin
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
| | - Shalini Desai
- Vaccine Preventable Diseases Section, Surveillance and Epidemiology Division, Centre for Immunization and Respiratory Infectious Diseases, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Averil Griffith
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada
| | - Laurence Caron-Poulin
- Vaccine Preventable Diseases Section, Surveillance and Epidemiology Division, Centre for Immunization and Respiratory Infectious Diseases, Public Health Agency of Canada, Ottawa, Ontario, Canada
| | - Brigitte Lefebvre
- Laboratoire de santé publique du Québec, Ste-Anne-de-Bellevue, Québec, Canada
| | - Allison McGeer
- Toronto Invasive Bacterial Diseases Network (TIBDN), Department of Microbiology, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Gregory J Tyrrell
- The Provincial Laboratory for Public Health (Microbiology), Edmonton, Alberta, Canada
| | - George G Zhanel
- Department of Medical Microbiology and Infectious Diseases, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | | | - Linda Hoang
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Paul N Levett
- Saskatchewan Disease Control Laboratory, Regina, Saskatchewan, Canada
| | | | - Rita Raafat Gad
- New Brunswick, Office of the Chief Medical Officer of Health, New Brunswick Department of Health, Fredericton, New Brunswick, Canada
| | - David Haldane
- Queen Elizabeth II Health Science Centre, Halifax, Nova Scotia, Canada
| | - George Zahariadis
- Newfoundland Public Health Laboratory, St. John's, Newfoundland and Labrador, Canada
| | - Gregory German
- Queen Elizabeth Hospital, Charlottetown, Prince Edward Island, Canada
| | | | - Lori Strudwick
- Yukon Communicable Disease Control, Government of Yukon, Whitehorse, Yukon, Canada
| | - Michael R Mulvey
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
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