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BACKGROUND: Streptococcus pneumoniae serotype 3 remains a problem globally. Malawi introduced 13-valent pneumococcal conjugate vaccine (PCV13) in 2011, but there has been no direct protection against serotype 3 carriage. We explored whether vaccine escape by serotype 3 is due to clonal expansion of a lineage with a competitive advantage. METHODS: The distribution of serotype 3 Global Pneumococcal Sequence Clusters (GPSCs) and sequence types (STs) globally was assessed using sequences from the Global Pneumococcal Sequencing Project. Whole-genome sequences of 135 serotype 3 carriage isolates from Blantyre, Malawi (2015-2019) were analyzed. Comparative analysis of the capsule locus, entire genomes, antimicrobial resistance, and phylogenetic reconstructions were undertaken. Opsonophagocytosis was evaluated using serum samples from vaccinated adults and children. RESULTS: Serotype 3 GPSC10-ST700 isolates were most prominent in Malawi. Compared with the prototypical serotype 3 capsular polysaccharide locus sequence, 6 genes are absent, with retention of capsule polysaccharide biosynthesis. This lineage is characterized by increased antimicrobial resistance and lower susceptibility to opsonophagocytic killing. CONCLUSIONS: A serotype 3 variant in Malawi has genotypic and phenotypic characteristics that could enhance vaccine escape and clonal expansion after post-PCV13 introduction. Genomic surveillance among high-burden populations is essential to improve the effectiveness of next-generation pneumococcal vaccines.
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Cápsulas Bacterianas , Filogenia , Infecções Pneumocócicas , Vacinas Pneumocócicas , Sorogrupo , Streptococcus pneumoniae , Humanos , Vacinas Pneumocócicas/imunologia , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/classificação , Infecções Pneumocócicas/prevenção & controle , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/imunologia , Cápsulas Bacterianas/imunologia , Cápsulas Bacterianas/genética , Malaui , Adulto , Sequenciamento Completo do Genoma , Pré-Escolar , Criança , Vacinas Conjugadas/imunologia , Masculino , Genoma Bacteriano , Feminino , Adulto Jovem , Lactente , Genótipo , Portador Sadio/microbiologiaRESUMO
BACKGROUND: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in U.S. children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts. METHODS: We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national healthcare surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses. RESULTS: Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval 1.8-3.9) visits and 2.4 (1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (11.2-20.4) visits and 13.2 (9.9-18.0) antibiotic prescriptions annually per 1,000 children. PCV15/20-additional serotypes account for 0.4% (0.2-0.6%) and 2.1% (1.5-3.0%) of pediatric outpatient antibiotic use. CONCLUSIONS: Compared with PCV15-additional serotypes, PCV20-additional serotypes account for >5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use.
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BACKGROUND: Pneumococcal carriage is associated with increased acquisition and duration of SARS-CoV-2 infection among adults. While pneumococcal conjugate vaccines (PCVs) prevent carriage of vaccine-serotype pneumococci, their potential impact on COVID-19 related outcomes remains poorly understood in populations with prevalent immunity against SARS-CoV-2. METHODS: We undertook a retrospective cohort study of adults aged ≥65 years in the Kaiser Permanente Southern California (KPSC) healthcare system who had received ≥2 COVID-19 vaccine doses, comparing risk of SARS-CoV-2 infection between 1 January, 2021 and 31 December, 2022 among recipients and non-recipients of PCV13. We estimated adjusted hazard ratios via Cox proportional hazards models, employing multiple strategies to mitigate bias from differential test-seeking behavior. RESULTS: The adjusted hazard ratio (aHR) of confirmed SARS-CoV-2 infection comparing PCV13 recipients to non-recipients was 0.92 (95% confidence interval: 0.90-0.95), corresponding to prevention of 3.9 (2.6-5.3) infections per 100 person-years. Following receipt of 2, 3, and ≥4 COVID-19 vaccine doses, aHRs were 0.85 (0.81-0.89), 0.94 (0.90-0.97), and 0.99 (0.93-1.04), respectively. The aHR for persons who had not received COVID-19 vaccination in the preceding 6 months was 0.90 (0.86-0.93), versus 0.94 (0.91-0.98) within 6 months after receipt of any dose. Similarly, the aHR was 0.92 (0.89-0.94) for persons without history of documented SARS-CoV-2 infection, versus 1.00 (0.90-1.12) for persons with documented prior infection. CONCLUSIONS: Among older adults who had received ≥2 COVID-19 vaccine doses, PCV13 was associated with modest protection against SARS-CoV-2 infection. Protective effects of PCV13 were greater among individuals expected to have weaker immune protection against SARS-CoV-2 infection.
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BACKGROUND: In addition to preventing pneumococcal disease, emerging evidence indicates that pneumococcal conjugate vaccines (PCVs) might indirectly reduce viral respiratory tract infections (RTI) by affecting pneumococcal-viral interactions. METHODS: We performed a systematic review of interventional and observational studies published during 2000-2022 on vaccine efficacy/adjusted effectiveness (VE) and overall effect of PCV7, PCV9, PCV10, or PCV13 against viral RTI. RESULTS: Sixteen of 1671 records identified were included. Thirteen publications described effects of PCVs against viral RTIs in children. VE against influenza ranged between 41-86% (n=4), except for the 2010-2011 influenza season. In a randomized controlled trial, PCV9 displayed efficacy against any viral RTI, human seasonal coronavirus, parainfluenza, and human metapneumovirus. Data in adults were limited (n=3). PCV13 VE ranged between 4-25% against viral lower RTI, 32-35% against COVID-19 outcomes, 24-51% against human seasonal coronavirus, and 13-36% against influenza A lower RTI, with some 95%CI spanning zero. No protection was found against adenovirus or rhinovirus in children or adults. CONCLUSIONS: PCVs were associated with protection against some viral RTI, with the strongest evidence for influenza in children. Limited evidence for adults was generally consistent with pediatric data. Restricting public health evaluations to confirmed pneumococcal outcomes may underestimate the full impact of PCVs.
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Starting in June 2016, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced into the routine immunization program of Mongolia by using a 2+1 dosing schedule, phased by district. We used prospective hospital surveillance to evaluate the vaccine's effect on pneumonia incidence rates among children 2-59 months of age over a 6-year period. Of 17,607 children with pneumonia, overall adjusted incidence rate ratios showed decreased primary endpoint pneumonia, very severe pneumonia, and probable pneumococcal pneumonia until June 2021. Results excluding and including the COVID-19 pandemic period were similar. Pneumonia declined in 3 districts that introduced PCV13 with catch-up campaigns but not in the 1 district that did not. After PCV13 introduction, vaccine-type pneumococcal carriage prevalence decreased by 44% and nonvaccine-type carriage increased by 49%. After PCV13 introduction in Mongolia, the incidence of more specific pneumonia endpoints declined in children 2-59 months of age; additional benefits were conferred by catch-up campaigns.
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Pandemias , Pneumonia Pneumocócica , Criança , Humanos , Vacinas Conjugadas , Incidência , Mongólia/epidemiologia , Estudos Prospectivos , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controleRESUMO
The Streptococcus pneumoniae bacteria has over 100 known serotypes that display a continuous change in prevalence by patients' age and geographical location and therefore necessitate continued efforts toward development of new vaccines with broader protection. Glycoconjugate vaccines have been instrumental in reducing global morbidity and mortality caused by Streptococcus pneumoniae infections. In these vaccines, the bacterial polysaccharide is conjugated to a carrier protein to enhance immunogenicity. To ensure well defined immunogenicity and stability of conjugated vaccines, reliable quantification of non-conjugated (free) polysaccharide is a critical, albeit challenging step during vaccine clinical dosing, release and stability monitoring. Multivalent preparations of Cross-reactive material 197 (CRM197)- conjugated pneumococcal polysaccharide materials often contain only nanogram levels of each individual free polysaccharide at final container concentrations. We have developed a novel method for the separation of free polysaccharides from conjugated material that requires no sample derivatization, employing instead an approach of quantitative immunoprecipitation of CRM197 with 3 different monoclonal antibodies and magnetic beads. A mix of antibodies against both linear and conformational epitopes enables successful removal of conjugates regardless of the protein folded state. The remaining free polysaccharide is subsequently measured in a serotype-specific ELISA.
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Polissacarídeos Bacterianos , Streptococcus pneumoniae , Humanos , Sorogrupo , Vacinas Conjugadas , Vacinas Pneumocócicas , Anticorpos AntibacterianosRESUMO
BACKGROUND: Bacterial meningitis is a rare, but life-threatening disease, which sometimes occurs as a complication to acute otitis media (AOM). The proportion of meningitis cases originating from AOM is not clear. PURPOSE: The aim of this study was to investigate the proportion of meningitis cases caused by AOM, to compare risk factors, bacteriology and outcome between otogenic and non-otogenic meningitis, and to analyse the incidence of bacterial meningitis after the introduction of conjugate pneumococcal vaccines (PCV). METHODS: The medical charts of all patients admitted to hospitals in southern Sweden with bacterial meningitis between 2000 and 2017 were retrieved. Based on otoscopy and/or imaging, the proportion of otogenic meningitis cases was calculated, as were annual incidences. RESULTS: A total of 216 patients were identified, 25 of whom died. The proportion of otogenic meningitis was 31% but varied from 6% among teenagers to 40% among adults. Before PCV, 23% of all meningitis cases were children < 2 years, compared to 1% post-PCV. The average incidence in the adult population, on the other hand, increased post-PCV, though there were large annual variations. S. pneumoniae was the most commonly identified pathogen in everyone but teenagers, in whom N. meningitidis was predominant. CONCLUSION: AOM is an important cause of meningitis in children and adults. Though bacterial meningitis almost disappeared in children < 2 years after the introduction of PCV, the incidence of pneumococcal meningitis in adults seems to have increased.
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Meningites Bacterianas , Otite Média , Humanos , Suécia/epidemiologia , Estudos Retrospectivos , Adolescente , Masculino , Feminino , Pré-Escolar , Adulto , Criança , Pessoa de Meia-Idade , Otite Média/epidemiologia , Otite Média/microbiologia , Idoso , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/microbiologia , Adulto Jovem , Lactente , Incidência , Fatores de Risco , Idoso de 80 Anos ou mais , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/isolamento & purificação , Neisseria meningitidis/isolamento & purificaçãoRESUMO
OBJECTIVES: Factors that affect the change of first-line antimicrobial agents were investigated to further promote their appropriate use. METHODS: This descriptive study used an electronic medical records database. Total 16,353 of the 199,896 patients enrolled between 1996 and 2019 met the inclusion criteria and formed the overall pediatric acute otitis media (AOM) cohort. The factors leading to the change in first-line antimicrobial agents within 14 days were analyzed using classification and regression trees (CART) analysis. RESULTS: This antimicrobial treatment cohort, involved 4860 cases of AOM alone and 9567 cases of AOM with other diseases. The size of the medical facility based on number of beds and historical duration of patient registration impacted on antimicrobial changes. CONCLUSIONS: The current results show that hospital-wide or nation-wide antimicrobial stewardship promotion could be the most influencing factor for antimicrobial changes. Particularly in cases of AOM where other diseases coexist, a more accurate diagnosis and definition of treatment failure of first-line drug are suggested to be important while establishing future treatment strategies. The current study is important to promote appropriate antimicrobial use for AOM treatment.
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Antibacterianos , Gestão de Antimicrobianos , Otite Média , Humanos , Otite Média/tratamento farmacológico , Otite Média/microbiologia , Estudos Retrospectivos , Japão , Gestão de Antimicrobianos/métodos , Feminino , Masculino , Pré-Escolar , Lactente , Antibacterianos/uso terapêutico , Doença Aguda , Criança , Anti-Infecciosos/uso terapêutico , Análise de Regressão , Registros Eletrônicos de Saúde/estatística & dados numéricosRESUMO
Pneumococcal conjugate vaccines (PCVs) have been developed to protect against pneumococcal diseases caused by the more than 100 serotypes of the bacterium Streptococcus pneumoniae. PCVs primarily prevent pneumococcal infections such as sepsis, bacteraemia, meningitis, otitis media, pneumonia, septicaemia, and sinusitis among infants, adults, elderly, and immunocompromised individuals. The current available PCVs only cover a limited number of serotypes, and there is an immense need for developing higher-valent PCVs that can protect against non-vaccine serotypes to overcome challenges like serotype replacement and antibiotic resistance. The main challenges for developing higher valent PCVs are the complexity of the manufacturing process comprising polysaccharide fermentation, purification, modification or sizing of multiple polysaccharides and conjugation between polysaccharides and carrier proteins, the stability of the conjugates, and the immunogenicity of the vaccine. Different manufacturing processes have been explored to produce higher valent PCVs using different serotypes of S. pneumoniae and conjugation with different carrier proteins. The global coverage of higher valent PCVs are still low, mainly due to the high cost and limited supply of the vaccine. This review focuses on the existing and emerging manufacturing processes and challenges associated with higher-valent pneumococcal PCV development.
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BACKGROUND: S. pneumoniae (SPN) is the most common cause of pneumonia. The disease can be effectively prevented through immunisation. Since December 2020, the Malaysian Government has included the 10-valent pneumococcal conjugate vaccine (PCV10) for all infants born on or after 1 January 2020 as part of the National Immunisation Programme (NIP). However, the epidemiology of pneumonia remains poorly understood. To fill the knowledge gap, we established a multicentre surveillance study to understand the burden of pneumococcal pneumonia among young children in Peninsular Malaysia. METHODS: MY-Pneumo is a multicentre prospective case-control study conducted in three sentinel sites located in three different states of Peninsular Malaysia - Kuala Lumpur, Pahang, and Kelantan. A cohort of at least 500 incident cases and 500 controls is enrolled beginning in October 2021 and matched for age. Cases are hospitalised children < 5 years with radiologically confirmed pneumonia, and the controls are children without any features suggestive of pneumonia. Clinical samples, including nasopharyngeal swabs (NPS) and urine, are collected according to the study protocol. Biological fluids such as blood, cerebrospinal fluid (CSF) and pleural fluid are obtained from invasive pneumonia disease (IPD) patients, if available. All children are tested for SPN using polymerase chain reaction (PCR) and pneumococcal urine antigen test (PUAT) using BinaxNow. DISCUSSION: Surveillance data, including carriage rate, serotype variations and the phylogeny data structure of SPN among young children in Malaysia during PCV implementation, will be generated from this study. Trends and patterns of pneumococcal serotypes by different regions are important for targeted public health strategies. Our data will provide baseline information for estimating the impact of PCV10 implementation and will influence policymakers' decisions regarding the upgrade from PCV10 to a higher-valency conjugate vaccine in Malaysia. TRIAL REGISTRATION: This project was registered at ClinicalTrials.gov (NCT04923035) on 2021, June 11. The study protocol was approved by the International Medical University Joint-Committee on Research & Ethics (4.15/JCM-216/2021) and the Institutional Review Board at sentinel sites (USM/JEPeM/21020190, IREC 2021-114, MREC ID No: 2021128-9769) and University of Southampton's Ethics and Research Governance (ERGo II 64844).
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Pneumonia Pneumocócica , Humanos , Malásia/epidemiologia , Estudos de Casos e Controles , Lactente , Pré-Escolar , Estudos Prospectivos , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Masculino , Streptococcus pneumoniae/isolamento & purificação , FemininoRESUMO
AIM: The pneumococcal conjugate vaccine, which covered seven serotypes of Streptococcus pneumoniae (PCV7), was introduced in Stockholm, Sweden, in 2007. It was replaced by a 13-valent vaccine (PCV13) in 2011. We previously reported a decreased incidence of pneumonia and sinusitis among young children 4 years after the introduction of the PCV7. This study followed the incidence of pneumonia, sinusitis, mastoiditis and meningitis for four more years. METHODS: We studied validated hospital registry data covering children up to 17 years of age, who were hospitalised in the Stockholm region from 2003 to 2016, when the child population peaked at 485 687. All 11 115 cases diagnosed with pneumonia, coded as bacterial pneumonia, sinusitis, mastoiditis, bacterial meningitis or empyema, were identified. The controls had viral pneumonia or pyelonephritis. RESULTS: The incidence rates for children under 2 years of age hospitalised for sinusitis, mastoiditis and meningitis decreased significantly by 61%-79% during the eight-year post-vaccination period. Hospitalisations for bacterial pneumonia decreased by 19%-25% in the same age group. These changes were probably due to both the vaccines and changes in diagnosis routines. CONCLUSION: The effect of vaccination on children under 2 years of age was sustained 8 years after the introduction of the pneumococcal conjugate vaccines.
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Mastoidite , Meningite , Infecções Pneumocócicas , Pneumonia Bacteriana , Pneumonia Viral , Sinusite , Criança , Humanos , Lactente , Pré-Escolar , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Vacina Pneumocócica Conjugada Heptavalente , Vacinas Conjugadas , Suécia/epidemiologia , Mastoidite/epidemiologiaRESUMO
Vaccination programs have proven successful in the prevention and control of infectious diseases among children on a global scale, but the majority of adult populations remain unvaccinated. immunocompromised adults as well as older adults aged low-income countries as Streptococcus pneumoniae infections are associated with substantial morbidity and mortality among 65 years and above. Despite the introduction of pneumococcal conjugate vaccines (PCVs), the burden of vaccine-type serotypes remains high in there are no clear policies for adult vaccination. As per the Global Burden of Disease 2019 report, about 120,000 individuals aged 70 years and older died as a result of LRTIs) in sub-Saharan Africa. A medical advisory board meeting was conducted in April 2022 to discuss the burden of pneumococcal diseases in adults, the current status of policies and practices of adult vaccination, unmet needs, and challenges in Ghana. This expert opinion paper outlines the pneumococcal epidemiology and burden of disease in Ghana, as well as the rationale for adult pneumococcal vaccination. It also highlights the potential barriers to adult vaccination and offers recommendations to overcome these obstacles and enhance vaccine acceptance in Ghana.
Les programmes de vaccination ont prouvé leur succès dans la prévention et le contrôle des maladies infectieuses chez les enfants à l'échelle mondiale, mais la majorité des populations adultes restent non vaccinées. Les infections à Streptococcus pneumoniae sont associées à une morbidité et une mortalité substantielles chez les adultes immunodéprimés ainsi que chez les personnes âgées de 65 ans et plus. Malgré l'introduction des vaccins conjugués contre le pneumocoque (VCP), la charge des sérotypes vaccinaux reste élevée dans les pays à faible revenu car il n'existe pas de politiques claires en matière de vaccination des adultes. Selon le rapport sur la charge mondiale de morbidité de 2019, environ 120 000 personnes âgées de 70 ans et plus sont décédées des suites d'infections des voies respiratoires inférieures (IVRI) en Afrique subsaharienne. Une réunion du conseil consultatif médical a eu lieu en avril 2022 pour discuter du fardeau des maladies pneumococciques chez les adultes, de l'état actuel des politiques et pratiques de vaccination des adultes, des besoins non satisfaits et des défis au Ghana. Cet article d'opinion d'experts présente l'épidémiologie pneumococcique et le fardeau de la maladie au Ghana, ainsi que les arguments en faveur de la vaccination pneumococcique des adultes. Il met également en lumière les obstacles potentiels à la vaccination des adultes et propose des recommandations pour surmonter ces obstacles et améliorer l'acceptation des vaccins au Ghana. MOTS-CLÉS: Maladie pneumococcique, Fardeau de la maladie, Vaccin conjugué contre le pneumocoque, Vaccination des adultes, Streptococcus pneumoniae, Ghana, Défis de la vaccination, Immunisation des adultes, VCP-13, Pneumonie acquise en communauté.
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Infecções Pneumocócicas , Vacinas Pneumocócicas , Vacinação , Humanos , Vacinas Pneumocócicas/administração & dosagem , Gana/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Infecções Pneumocócicas/epidemiologia , Adulto , Idoso , Vacinas Conjugadas/administração & dosagem , Streptococcus pneumoniae/imunologia , Programas de Imunização , Prova PericialRESUMO
BACKGROUND: Interactions of Streptococcus pneumoniae with viruses feature in the pathogenesis of numerous respiratory illnesses. METHODS: We undertook a case-control study among adults at Kaiser Permanente Southern California between 2015 and 2019. Case patients had diagnoses of lower respiratory tract infection (LRTI; including pneumonia or nonpneumonia LRTI diagnoses), with viral infections detected by multiplex polymerase chain reaction testing. Controls without LRTI diagnoses were matched to case patients by demographic and clinical attributes. We measured vaccine effectiveness (VE) for 13-valent (PCV13) against virus-associated LRTI by determining the adjusted odds ratio for PCV13 receipt, comparing case patients and controls. RESULTS: Primary analyses included 13 856 case patients with virus-associated LRTI and 227 887 matched controls. Receipt of PCV13 was associated with a VE of 24.9% (95% confidence interval, 18.4%-30.9%) against virus-associated pneumonia and 21.5% (10.9%-30.9%) against other (nonpneumonia) virus-associated LRTIs. We estimated VEs of 26.8% (95% confidence interval, 19.9%-33.1%) and 18.6% (9.3%-27.0%) against all virus-associated LRTI episodes diagnosed in inpatient and outpatient settings, respectively. We identified statistically significant protection against LRTI episodes associated with influenza A and B viruses, endemic human coronaviruses, parainfluenza viruses, human metapneumovirus, and enteroviruses but not respiratory syncytial virus or adenoviruses. CONCLUSIONS: Among adults, PCV13 conferred moderate protection against virus-associated LRTI. The impacts of pneumococcal conjugate vaccines may be mediated, in part, by effects on polymicrobial interactions between pneumococci and respiratory viruses.
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Infecções Pneumocócicas , Pneumonia Pneumocócica , Pneumonia , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Vírus , Humanos , Adulto , Estudos de Casos e Controles , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controle , Streptococcus pneumoniae , Vacinação , Vacinas Conjugadas , Vacinas Pneumocócicas , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controleRESUMO
BACKGROUND: Updated recommendations of the US Advisory Committee on Immunization Practices indicate that all adults aged ≥65 years and adults aged <65 years with comorbid conditions should receive 15- and 20-valent pneumococcal conjugate vaccines (PCV15/20). We aimed to assess the potential impact of these recommendations on the burden of lower respiratory tract infections (LRTIs) among adults. METHODS: We estimated the incidence of LRTI cases and associated hospital admissions among enrollees of Kaiser Permanente Southern California from 2016 through 2019. We used a counterfactual inference framework to estimate excess LRTI-associated risk of death up to 180 days after diagnosis. We used prior estimates of PCV13 effectiveness against LRTI to model potential direct effects of PCV15/20 by age group and risk status. RESULTS: Use of PCV15 and PCV20, respectively, could prevent 89.3 (95% confidence interval, 41.3-131.8) and 108.6 (50.4-159.1) medically attended LRTI cases; 21.9 (10.1-32.0) and 26.6 (12.4-38.7) hospitalized LRTI cases; and 7.1 (3.3-10.5) and 8.7 (4.0-12.7) excess LRTI-associated deaths, each per 10 000 person-years. Among at-risk adults aged <65 years, use of PCV15 and PCV20 could prevent 85.7 (39.6-131.5) and 102.7 (47.8-156.7) medically attended LRTI cases per 10 000 person-years; 5.1 (2.4-8.6) and 6.2 (2.8-10.2) LRTI hospitalizations per 10 000 person-years, and 0.9 (0.4-1.4) and 1.1 (0.5-1.7) excess LRTI-associated deaths per 10 000 person-years. CONCLUSIONS: Our findings suggest recent recommendations, including PCV15/20 within adult pneumococcal vaccine series, may substantially reduce LRTI burden.
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Infecções Pneumocócicas , Infecções Respiratórias , Humanos , Adulto , Estados Unidos/epidemiologia , Adolescente , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Streptococcus pneumoniae , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controle , Imunização , Vacinas Pneumocócicas , Vacinas ConjugadasRESUMO
Streptococcus pneumoniae is a highly invasive bacterial pathogen that can cause a range of illnesses. Pneumococcal capsular polysaccharides (CPS) are the main virulence factors that causes invasive pneumococcal disease (IPD). Pneumococcal CPS serotype 7F along with a few other serotypes is more invasive and likely to cause IPD. Therefore, 7F is a target for pneumococcal vaccine development, and is included in the two recently approved multi-valent pneumococcal conjugated vaccines, i.e. VAXNEUVANCE and PREVNAR 20.To support process and development of our 15-valent pneumococcal conjugated vaccine (PCV15), chromatographic methods have been developed for 7F polysaccharide and conjugate characterization. A size-exclusion chromatography (SEC) method with UV, light scattering and refractive index detections was employed for concentration, size and conformation analysis. A reversed-phase ultra-performance liquid chromatography (RP-UPLC) method was used for analysis of conjugate monosaccharide composition and degree of conjugation. The collective information obtained by these chromatographic analysis provided insights into the pneumococcal conjugate and conjugation process.
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Infecções Pneumocócicas , Humanos , Sorogrupo , Sorotipagem , Infecções Pneumocócicas/prevenção & controle , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae , Vacinas Pneumocócicas , Vacinas Conjugadas , Antígenos de BactériasRESUMO
OBJECTIVE: A combination of 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) is currently recommended for adults with systemic lupus erythematosus (SLE). However, data on the immunogenicity elicited by sequential pneumococcal vaccination in this patient population are scarce. In this study, we compared short-term antibody responses to both PCV13/PPSV23 (≥8-week interval) and PPSV23/PCV13 (≥12-month interval) vaccination strategies in pneumococcal vaccine-naive adults with SLE. METHODS: This longitudinal, open-label, quasi-randomized study was performed in a single-center cohort of adults (18 years or older) with SLE. In both vaccination groups, blood samples were collected immediately before administering the first dose of the pneumococcal vaccine (timepoint T0), 4-6 weeks after the priming dose (T1), and 4-6 weeks after the booster dose (T2). We focused on the 12 shared serotypes between PCV13 and PPSV23, and compared the following immunogenicity outcomes between the groups at T2: anti-pneumococcal antibody geometric mean concentration (ApAb GMC), fold increase in ApAb levels (FI-ApAb), overall seroprotection rate, and overall seroconversion rate. The protective level for each pneumococcal serotype was set at 1.3 µg/mL. We used the multi-analyte immunodetection method to determine serum levels of ApAbs. RESULTS: Thirty-four patients with SLE were screened between April 2019 and January 2020, and 16 of them (mean age: 39.4 years, 87.5% female, and 100% on immunosuppressants) had evaluable immunogenicity results at T2. The median time elapsed between the pneumococcal vaccinations was 56 days in the PCV13/PPSV23 group (n = 11 patients) and 16 months in the PPSV23/PCV13 group (n = 5 patients). Priming with PCV13 (PCV13/PPSV23 group), as opposed to PPSV23 (PPSV23/PCV13 group), yielded significantly better results regarding FI-ApAb, overall seroconversion rate, and overall seroprotection rate 4-6 weeks after each pneumococcal vaccination. A trend toward augmented ApAb GMC in the patients who received the PCV13/PPSV23 sequence was also observed. No relevant safety issues were identified with sequential pneumococcal vaccination. CONCLUSION: The PCV13-priming PPSV23-boost strategy in adults with SLE induced greater antibody responses for most immunogenicity outcomes than those elicited by the PPSV23/PCV13 strategy.
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Lúpus Eritematoso Sistêmico , Infecções Pneumocócicas , Adulto , Feminino , Humanos , Masculino , Anticorpos Antibacterianos , Brasil , Estudos de Coortes , Método Duplo-Cego , Imunogenicidade da Vacina , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Vacinação , Vacinas ConjugadasRESUMO
OBJECTIVES: Pneumococcal conjugate vaccines (PCVs) have significantly reduced disease burden caused by Streptococcus pneumoniae, a leading cause of childhood morbidity and mortality globally. This systematic review and meta-analysis aimed to assess the incremental net benefit (INB) of the 13-valent PCV (PCV13) and 10-valent PCV (PCV10) in children. METHODS: We performed a comprehensive search in several databases published before May 2022. Studies were included if they were cost-effectiveness or cost-utility analyses of PCV13 or PCV10 compared with no vaccination or with each other in children. Various monetary units were converted to purchasing power parity, adjusted to 2021 US dollars. The INBs were calculated and then pooled across studies stratified by country income level, perspective, and consideration of herd effects, using a random-effect model. RESULTS: Seventy studies were included. When herd effects were considered, PCV13 was cost-effective compared with PCV10 from the payer perspective in both high-income countries (HICs) (INB, $103.94; 95% confidence interval, $75.28-$132.60) and low- and middle-income countries (LMICs) (INB, $53.49; 95% confidence interval, $30.42-$76.55) with statistical significance. These findings were robust across a series of sensitivity analyses. PCV13 was cost-effective compared with no vaccination across perspectives and consideration of herd effects in both HICs and LMICs, whereas findings were less consistent for PCV10. CONCLUSION: PCVs were generally cost-effective compared with no vaccination in HICs and LMICs. Our study found that PCV13 was cost-effective compared with PCV10 when herd effects were considered from the payer perspective in both HICs and LMICs. The results are sensitive to the consideration of herd effects.
Assuntos
Infecções Pneumocócicas , Criança , Humanos , Lactente , Infecções Pneumocócicas/prevenção & controle , Análise Custo-Benefício , Programas de Imunização , Vacinação , Vacinas Pneumocócicas/uso terapêutico , Vacinas ConjugadasRESUMO
BACKGROUND: Streptococcus pneumoniae (S. pneumoniae), remains a major cause of mortality and morbidity worldwide. The objective of this study was to determine the trends of invasive pneumococcal diseases (IPD) in adult and elderly population in Casablanca (Morocco) before and after introduction of pneumococcal conjugate vaccine (PCV) by determining the distribution of pneumococcal serotypes and antibiotic resistance profile of isolated strains. METHOD: The proposed study is a retrospective laboratory-based surveillance of IPD in hospitalized adult (15-59 years old) and elderly (≥ 60 years old) patients in Ibn Rochd University Hospital Centre from 2007 to 2019 (13 years). All the 250 non-duplicate clinical invasive isolates from adult and elderly patients, confirmed as S. pneumoniae according to the laboratory standard identification procedures, are included in this study. RESULTS: A significant decrease of the overall incidence in IPD was observed only in adults from 0.71 to 0.54/100000 populations (P = 0.02) and to 0.47/100000 populations (P = 0.0137) in the early and mature post-vaccine period respectively compared to the pre-vaccine period. Our results also showed a significant reduction in the overall prevalence of vaccine serotypes from 28.17 to 6.90% (P = 0.0021) for the PCV-10 serotypes, and from 46.48 to 25.86% (P = 0.0164) for the PCV-13 serotypes only in the mature post-vaccine period (2015-2019). In parallel, the rate of non-vaccine serotypes did not significantly change in the early post-vaccine period (2011-2014) while it increased considerably from 54 to 74.14% (P = 0.0189) during the mature post-vaccine period. The rate of penicillin non-susceptible pneumococcal isolates decreased significantly from 23.94 to 8.77% (P = 0.02) in adult patients, and the rate of cotrimoxazole non-susceptible pneumococcal isolates significantly decreased from 29.58 to 8.77% in the early post-vaccine period (P = 0.003) and to 7.24% in the mature post-vaccine period (P = 0.0007). CONCLUSION: Although childhood vaccination has considerably reduced the incidence of IPD in adult population through the herd effect, IPD remain a real public health problem due to the alarming increase in non-vaccine serotypes (NVS) and the lack of herd effect among elderly population. The rate of antibiotic resistance was relatively low. Nevertheless, resistance constitutes a serious problem to the therapeutic arsenal due to the known capacity for genetic dissemination in the pneumococcus.
Assuntos
Anti-Infecciosos , Infecções Pneumocócicas , Humanos , Adulto , Idoso , Lactente , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Streptococcus pneumoniae , Sorogrupo , Vacinas Conjugadas , Marrocos/epidemiologia , Estudos Retrospectivos , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , SorotipagemRESUMO
BACKGROUND: The morbidity and mortality of adult diseases caused by S. pneumoniae increase with age and presence of underlying chronic diseases. Currently, two vaccine technologies against S. pneumoniae are used: the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the pneumococcal conjugate vaccines, one of which is the 20-valent pneumococcal conjugate vaccine (PCV20) that has recently been approved for adults. OBJECTIVE: This study was conducted to investigate the cost-effectiveness of implementing PCV20 in a reimbursement scheme for Norwegian adults aged 18-99 years at risk of pneumococcal diseases and those aged 65 years and older at low risk compared to PPV23. METHODS: An established Markov model was adapted to a Norwegian setting to estimate the economic and clinical consequences of vaccinating the Norwegian population in specific age and risk groups against pneumococcal diseases. Inputs for the model were found in Norwegian or Danish real-world evidence or retrieved from available studies. The costs and clinical outcomes were assessed using a health sector perspective and a lifetime time horizon. RESULTS: The results showed that PCV20 was associated with better health outcomes including fewer disease cases, fewer disease-attributable fatalities, a higher gain of life years and quality-adjusted life years compared to PPV23. In addition, PCV20 had a lower total cost compared to PPV23. Therefore, PCV20 was the dominant vaccination strategy. The base case result was investigated in multiple sensitivity analyses, which showed that the results were robust to changes in input parameters and methodological assumptions, as PCV20 remained the dominant vaccination strategy in almost all scenarios. CONCLUSION: Results showed that vaccinating the Norwegian adults with PCV20 was cost-effective compared to PPV23. Changes in the hospital cost of pneumonia, the price of PCV 20, the effectiveness of PCV20 against pneumonia, and the pneumonia disease incidence had the highest impact on the ICER, i.e., were the main drivers of the results.
RESUMO
To examine the impact of pneumococcal conjugate vaccines (PCV) on the occurrence of recurrent acute otitis media (rAOM) among infants diagnosed with an early acute otitis media (AOM) episode. Retrospective cohort study of pediatric patients with a first episode of AOM at an age < 2 months. Data included clinical, demographic, and microbiological findings at the first AOM episode. In addition, a 5-year follow-up after the patient's first episode was completed from the medical records. This information included documentation of rAOM episodes and complications of AOM (hearing loss, speech disturbance, mastoiditis, and tympanic membrane perforation) and of ear-related surgical procedures (ventilation tube placement, adenoidectomies, and mastoid surgery). Two groups were studied: patients diagnosed between 2005 and 2009 (representing the unvaccinated group, group 1) and those diagnosed in 2010-2014 (the vaccinated group, group 2). A total of 170 infants were diagnosed with a first AOM episode at an age < 2 months; 81 of them belonged to group 1 and 89 to group 2. Streptococcus pneumoniae was isolated in the middle-ear fluid in the first AOM episode in 48.1% of the patients in group 1 and in 30.3% in group 2 (P = 0.0316). 49/81 (60.5%) infants in group 1 were diagnosed with rAOM versus 39/80 (43.8%) in group 2 (P = 0.0298). No statistical differences were found between the groups with respect to long-term complications or need for surgery later in life. Conclusion: Our study showed a significant decrease in the occurrence of rAOM in infants diagnosed with AOM during the first 2 months of life and timely immunized with PCVs following this initial AOM episode. What is Known: ⢠30% of children experience recurrent AOM (rAOM) at the first year of life. The earlier the age of the first AOM, the greater the risk for future complications. ⢠After the introduction of PCVs, the overall pneumococcal AOM incidence declined. We investigated the future effect of PCVs on rAOM occurrence, when administered after the first AOM episode. What is New: ⢠A retrospective cohort of 170 infants with a first AOM episode at an age <2 months and followed for 5 years, showed a significant decrease (28.0%) of rAOM in immunized infants following the initial AOM episode. ⢠Our findings supplement previous data suggesting that the widespread PCVs use prevents rAOM by preventing early AOM and emphasize the importance of timely administration of the PCVs.