RESUMO
Streptococcus pneumoniae is a bacterium of great global importance, responsible for more than one million deaths per year. This bacterium is commonly acquired in the first years of life and colonizes the upper respiratory tract asymptomatically by forming biofilms that persist for extended times in the nasopharynx. However, under conditions that alter the bacterial environment, such as viral infections, pneumococci can escape from the biofilm and invade other niches, causing local and systemic disease of varying severity. The polyamine transporter PotABCD is required for optimal survival of the organism in the host. Immunization of mice with recombinant PotD can reduce subsequent bacterial colonization. PotD has also been suggested to be involved in pneumococcal biofilm development. Therefore, in this study we aimed to elucidate the role of PotABCD and polyamines in pneumococcal biofilm formation. First, the formation of biofilms was evaluated in the presence of exogenous polyamines-the substrate transported by PotABCD-added to culture medium. Next, a potABCD-negative strain was used to determine biofilm formation in different model systems using diverse levels of complexity from abiotic surface to cell substrate to in vivo animal models and was compared with its wild-type strain. The results showed that adding more polyamines to the medium stimulated biofilm formation, suggesting a direct correlation between polyamines and biofilm formation. Also, deletion of potABCD operon impaired biofilm formation in all models tested. Interestingly, more differences between wild-type and mutant strains were observed in the more complex model, which emphasizes the significance of employing more physiological models in studying biofilm formation.
Assuntos
Biofilmes , Streptococcus pneumoniae , Biofilmes/crescimento & desenvolvimento , Streptococcus pneumoniae/fisiologia , Streptococcus pneumoniae/metabolismo , Animais , Camundongos , Poliaminas/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Infecções Pneumocócicas/microbiologia , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/genética , ÓperonRESUMO
BACKGROUND: Streptococcus pneumoniae bacteremia may result in Infective Endocarditis (IE). In the pre-antibiotic era, it caused 10 %â15 % of IE, decreasing to < 3 % after penicillin availability. Although infrequent, it causes aggressive disease. METHODS: Retrospective analysis of endocarditis databases, prospectively implemented in 4 Brazilian institutions, 2005â2023. RESULTS: From the prospective cohorts comprising 2321 adult patients with IE, we identified 11 (0.47%) with pneumococcal IE. Males represented 7/11 and mean age was 54 years (22â77). All had native valve involvement; perivalvular abscess was present in 6/11. Only one patient had concurrent meningitis. Beta-lactams were the antibiotics used in 10/11. All had surgical indication, but only 6 had it, as the others were seriously ill. Overall, in hospital mortality was 6/11, but only 1/6 of those who underwent surgery died, compared to 5/5 of those who had an indication for surgery and did not have it. CONCLUSIONS: The high mortality rates and need for surgical intervention emphasize the need to promptly identify and manage pneumococcal endocarditis. Physicians ought to recommend vaccination to all patients at risk for severe pneumococcal disease.
Assuntos
Endocardite Bacteriana , Infecções Pneumocócicas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Brasil/epidemiologia , Adulto , Idoso , Infecções Pneumocócicas/mortalidade , Infecções Pneumocócicas/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/mortalidade , Estudos Retrospectivos , Adulto Jovem , Antibacterianos/uso terapêutico , Mortalidade Hospitalar , Streptococcus pneumoniae/isolamento & purificação , Índice de Gravidade de Doença , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVES: The 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for infants in Argentina's national immunization program (NIP) in a 2 + 1 schedule since 2012. Licensure of the 15-valent vaccine (PCV15) is anticipated soon, and the 20-valent vaccine (PCV20) recently received regulatory approval. This cost-effectiveness analysis examined the public health and economic implications of transitioning from PCV13 to either PCV15 or PCV20 in Argentina's pediatric NIP. METHODS: A decision-analytic Markov model was used with a 10-year time horizon and a 3.0% annual discount rate for costs and benefits. Vaccine effectiveness estimates were derived from Argentinian surveillance data, PCV13 clinical effectiveness and impact studies, and PCV7 efficacy studies. Population, epidemiologic, and economic inputs were obtained from literature and Argentinian-specific data. The study adopted a healthcare system perspective; sensitivity and scenario analyses were conducted to assess input parameters and structural uncertainty. RESULTS: Compared with PCV13, PCV20 was estimated to avert an additional 7,378, 42,884, and 172,389 cases of invasive pneumococcal disease (IPD), all-cause pneumonia, and all-cause otitis media (OM), respectively, as well as 3,308 deaths, resulting in savings of United States Dollars (USD) 50,973,962 in direct medical costs. Compared with PCV15, PCV20 was also estimated to have greater benefit, averting an additional 6,140, 35,258, and 142,366 cases of IPD, pneumonia, and OM, respectively, as well as 2,624 deaths, resulting in savings of USD 37,697,868 in direct medical costs. PCV20 was associated with a higher quality-adjusted life year gain and a lower cost (i.e., dominance) versus both PCV13 and PCV15. Results remained robust in sensitivity analyses and scenario assessments. CONCLUSION: Over a 10-year horizon, vaccination with PCV20 was expected to be the dominant, cost-saving strategy versus PCV13 and PCV15 in children in Argentina. Policymakers should consider the PCV20 vaccination strategy to achieve the greatest clinical and economic benefit compared with lower-valent options.
Assuntos
Análise Custo-Benefício , Infecções Pneumocócicas , Vacinas Pneumocócicas , Vacinas Conjugadas , Vacinas Pneumocócicas/economia , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/imunologia , Humanos , Argentina/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Infecções Pneumocócicas/economia , Infecções Pneumocócicas/epidemiologia , Lactente , Vacinas Conjugadas/economia , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia , Pré-Escolar , Programas de Imunização/economia , Cadeias de Markov , Anos de Vida Ajustados por Qualidade de Vida , Criança , Feminino , Masculino , Análise de Custo-EfetividadeRESUMO
BACKGROUND: Invasive pneumococcal diseases (IPD) are associated with high morbidity, mortality, and health costs worldwide, particularly in Latin America and the Caribbean (LAC). Surveillance about the distribution of serotypes causing IPD and the impact of pneumococcal vaccination is an important epidemiological tool to monitor disease activity trends, inform public health decision-making, and implement relevant prevention and control measures. OBJECTIVES: To estimate the serotype distribution for IPD and the related disease burden in LAC before, during, and after implementing the pneumococcal vaccine immunization program in LAC. METHODS: Systematic literature review following Cochrane methods of studies from LAC. We evaluated the impact of the pneumococcal vaccine on hospitalization and death during or after hospitalizations due to pneumococcal disease and serotype-specific disease over time. We also analyzed the incidence of serotyped IPD in pneumococcal conjugate vaccine PCV10 and PCV13. The protocol was registered in PROSPERO (ID: CRD42023392097). RESULTS: 155 epidemiological studies were screened and provided epidemiological data on IPD. Meta-analysis of invasive diseases in children <5 years old found that 57%-65% of causative serotypes were included in PCV10 and 66%-84% in PCV13. After PCV introduction, vaccine serotypes declined in IPD, and the emergence of non-vaccine serotypes varied by country. CONCLUSIONS: Pneumococcal conjugate vaccines significantly reduced IPD and shifted serotype distribution in Latin America and the Caribbean. PCV10/PCV13 covered 57-84% of serotypes in children under 5, with marked decline in PCV serotypes post-vaccination. Continuous surveillance remains crucial for monitoring evolving serotypes and informing public health action.
Assuntos
Infecções Pneumocócicas , Vacinas Pneumocócicas , Sorogrupo , Streptococcus pneumoniae , Humanos , América Latina/epidemiologia , Região do Caribe/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/imunologia , Vacinas Pneumocócicas/uso terapêutico , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/classificação , Vacinação , Efeitos Psicossociais da Doença , IncidênciaRESUMO
BACKGROUND: Streptococcus pneumoniae is a leading cause of morbidity and mortality globally, causing bacteremic pneumonia, meningitis, sepsis, and other invasive pneumococcal diseases. Evidence supports nasopharyngeal pneumococcal carriage as a reservoir for transmission and precursor of pneumococcal disease. OBJECTIVES: To estimate the pneumococcal nasopharyngeal burden in all age groups in Latin America and the Caribbean (LAC) before, during, and after the introduction of pneumococcal vaccine conjugate (PVC). METHODS: Systematic literature review of international, regional, and country-published and unpublished data, together with reports including data from serotype distribution in nasopharyngeal carriage in children and adults from LAC countries following Cochrane methods. The protocol was registered in PROSPERO database (ID: CRD42023392097). RESULTS: We included 54 studies with data on nasopharyngeal pneumococcal carriage and serotypes from 31,803 patients. In children under five years old, carriage was found in 41% and in adults over 65, it was 26%. During the study period, children under five showed a colonization proportion of 34% with PCV10 serotypes and 45% with PCV13 serotypes. When we analyze the carriage prevalence of PCV serotypes in all age groups between 1995 and 2019, serotypes included in PCV10 and those included in PCV13, both showed a decreasing trend along analysis by lustrum. CONCLUSION: The data presented in this study highlights the need to establish national surveillance programs to monitor pneumococcal nasopharyngeal carriage to monitor serotype prevalence and replacement before and after including new pneumococcal vaccines in the region. In addition, to analyze differences in the prevalence of serotypes between countries, emphasize the importance of approaches to local realities to reduce IPD effectively.
Assuntos
Portador Sadio , Nasofaringe , Infecções Pneumocócicas , Vacinas Pneumocócicas , Streptococcus pneumoniae , Humanos , Streptococcus pneumoniae/isolamento & purificação , América Latina/epidemiologia , Região do Caribe/epidemiologia , Nasofaringe/microbiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Infecções Pneumocócicas/microbiologia , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Vacinas Pneumocócicas/administração & dosagem , Sorogrupo , Pré-Escolar , Adulto , Criança , PrevalênciaRESUMO
BACKGROUND: Streptococcus pneumoniae (Spn) is a commensal pathogen that usually colonizes the upper respiratory tract of children. Likewise, Spn colonization has been considered a critical factor in the development of pneumococcal invasive disease. However, Spn prevalence in adults remains unclear. This study performs a systematic review and meta-analysis to explore the prevalence of Spn Nasopharynx - Oropharynx Colonization (NOC) in adults. METHODS: A Systematic review of scientific databases was utilized to identify eligible studies that follow strict selection criteria. Subsequently, a meta-analysis was conducted to establish NOC prevalence in adults (≥18 years old). The heterogeneity and sensitivity analyses were assessed using the microorganism identification technique, sample type, and age subgroups. RESULTS: Initial selection includes 69 studies, with 37 selected for the meta-analysis, involving 23,724 individuals. The overall prevalence (95 % CI) of Spn NOC among adults was 6 % (5-9). The subgroup analysis revealed that young adults (YA), 18-64 years old, had a prevalence of 10 %, whereas older adults (OA), ≥65 years old, had a prevalence of 2 %. The identification of Spn NOC may vary depending on the method of diagnosis used. High heterogeneity (I2 > 90 %) was observed but diminished to 70 % when the analysis was restricted to oropharyngeal swabs as an identification method. Furthermore, heterogeneity decreased to 58 % when exclusively employing traditional culture as the identification method. CONCLUSIONS: This study found a low prevalence of Spn NOC in adults. Notably, the prevalence of Spn NOC was higher in younger adults than in older adults. It is essential to highlight a significant heterogeneity among studies, which indicates there is no standardized method of Spn NOC identification.
Assuntos
Portador Sadio , Nasofaringe , Orofaringe , Infecções Pneumocócicas , Streptococcus pneumoniae , Humanos , Nasofaringe/microbiologia , Orofaringe/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Adulto , Prevalência , Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Pessoa de Meia-Idade , Adulto Jovem , Idoso , AdolescenteRESUMO
BACKGROUND: Understanding the epidemiology of Streptococcus pneumoniae (S. pneumoniae) isolates is important for pneumonia treatment and prevention. This research aimed to explore the epidemiological characteristics of S. pneumoniae isolated from pediatric inpatients and outpatients during the same period. METHODS: S. pneumoniae were isolated from unsterile samples of inpatients and outpatients younger than five years old between March 2013 and February 2014. The serotypes were determined using diagnostic pneumococcal antisera. The resistance of each strain to 13 antibiotics was tested using either the E-test or the disc diffusion method. The Sequence Types (STs) were analyzed via Multilocus Sequence Typing (MLST). RESULTS: The dominant serotypes obtained from inpatients were 19F (32.9 %), 19A (20.7 %), 23F (10.7 %), 6A (10.0 %), and 14 (8.6 %), while those from outpatients were 19F (13.6 %), 23F (12.9 %), 6A (10.0 %), 6B (10.0 %), and 19A (7.9 %). The coverage rates of 13-valent Pneumococcal Conjugate Vaccine (PCV) formulations were high in both groups. The nonsusceptibility to penicillin, cefuroxime, imipenem, erythromycin, and trimethoprim-sulfamethoxazole among the inpatient isolates was 7.1 %, 92.8 %, 65.7 %, 100 %, and 85.0 %, respectively, while that among the outpatient isolates was 0.7 %, 50.0 %, 38.6 %, 96.4 %, and 65.7 %, respectively. There were 45 and 81 STs detected from the pneumococci isolated from inpatients and outpatients, respectively. CC271 was common among both inpatients and outpatients (43.6 % and 14.3 %). CONCLUSIONS: Pneumococcal vaccine-related serotypes are prevalent among both inpatients and outpatients, especially among inpatients, who exhibit more severe antibiotic resistance. Therefore, universal immunization with PCV13 would decrease the hospitalization rate due to S. pneumoniae and the antibiotic resistance rate of S. pneumoniae.
Assuntos
Antibacterianos , Pacientes Internados , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Pacientes Ambulatoriais , Infecções Pneumocócicas , Sorogrupo , Streptococcus pneumoniae , Humanos , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/genética , Pré-Escolar , Pacientes Ambulatoriais/estatística & dados numéricos , Lactente , Antibacterianos/farmacologia , Masculino , Feminino , Pacientes Internados/estatística & dados numéricos , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/epidemiologia , Hospitais Pediátricos , Farmacorresistência Bacteriana , Pequim/epidemiologia , Sorotipagem , Vacinas Pneumocócicas/imunologiaRESUMO
PURPOSE: To provide information about which pneumococcal vaccine could have greater coverage in Colombia. METHODS: This is a retrospective analysis of patients diagnosed with invasive pneumococcal disease (IPD) between 2015 and 2019 in Bogotá, Colombia. We compared the theoretical serotype coverage of the available anti-pneumococcal vaccines (i.e., PCV-10, PCV-10 SII, PCV-13, PCV-15, PCV-20, PCV-21, PCV24, PPSV-23) and the non-vaccine-covered serotypes stratified by age. RESULTS: 690 IPD cases were included. In children ≤5 y/o, of the approved vaccines PCV-20 showed the most theoretical protection (71.3 % [149/209]), while in adults aged 18-64 y/o was PCV-20 (61.8 % [164/265]), and in those ≥65 y/o was PPSV-23 (58.1 % [100/172]) followed by PCV-20 (55.2 % [95/172]). The non-covered serotypes represented one-third of the cohort (33.9 % [234/690]), being 6C (20.5 % [48/234]), 15A (12.8 % [30/234]), and 23A (11.5 % [27/234]) the most prevalent. CONCLUSION: Introducing PCV-20 for children and PCV-20 along with a PPSV-23 booster in adults may reduce IPD frequency in all ages in Colombia. The inclusion of non-covered serotypes is required for future vaccines.
Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Adulto , Criança , Humanos , Lactente , Colômbia/epidemiologia , Estudos Retrospectivos , Vacinação , Vacinas Conjugadas/uso terapêutico , Vacinas Pneumocócicas/uso terapêutico , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , SorogrupoRESUMO
Streptococcus pneumoniae is an important human pathogen. Currently used conjugate vaccines are effective against invasive disease, but protection is restricted to serotypes included in the formulation, leading to serotype replacement. Furthermore, protection against non-invasive disease is reported to be considerably lower. The development of a serotype-independent vaccine is thus important and Pneumococcal surface protein A (PspA) is a promising vaccine candidate. PspA shows some diversity and can be classified in 6 clades and 3 families, with families 1 and 2 being the most frequent in clinical isolates. The ideal vaccine should thus induce protection against the two most common families of PspA. The aim of this work was to develop a liposome-based vaccine containing PspAs from family 1 and 2 and to characterize its immune response. Liposomes (LP) composed of dipalmitoylphosphatidylcholine (DPPC) and 3ß-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol) with or without α-galactosylceramide (α-GalCer) were produced by microfluidics, encapsulating PspA from clade 1 (PspA1, family 1) and/or clade 4 (PspA4Pro, family 2) followed by spray-drying with trehalose to form nanocomposite microparticles carriers (NCMP). LP/NCMPs showed good stability and preservation of protein activity. LP/NCMPs containing PspA1 and/or PspA4Pro were used for immunization of mice targeting the lungs. High serum IgG antibody titers against both PspA1 and PspA4Pro were detected in animals immunized with LP/NCMPs containing α-GalCer, with a balance of IgG1 and IgG2a titers. IgG in sera from immunized mice bound to pneumococcal strains from different serotypes and expressing different PspA clades, indicating broad recognition. Mucosal IgG and IgA were also detected. Importantly, immunization with LP/NCMPs induced full protection against strains expressing PspAs from family 1 and 2. Furthermore, CD4+ resident memory T cells were detected in the lungs of the immunized animals that survived the challenge.
Assuntos
Galactosilceramidas , Infecções Pneumocócicas , Streptococcus pneumoniae , Humanos , Animais , Camundongos , Lipossomos , Pós , Infecções Pneumocócicas/prevenção & controle , Proteínas de Bactérias , Imunização , Vacinas Pneumocócicas , Imunoglobulina G , Pulmão , Anticorpos Antibacterianos , Camundongos Endogâmicos BALB CRESUMO
Background: Invasive pneumococcal disease has declined since pneumococcal conjugate vaccine introduction in Latin America and the Caribbean (LAC). However, serotype distribution and antimicrobial resistance patterns have changed. Methods: We conducted a systematic review to evaluate the frequency of antimicrobial resistance of Streptococcus pneumoniae from invasive disease in LAC. Articles published between 1 January 2000, and 27 December 2022, with no language restriction, were searched in major databases and gray literature. Pairs of reviewers independently selected extracted data and assessed the risk of bias in the studies. The quality of antimicrobial resistance (AMR) studies was evaluated according to WHO recommendations (PROSPERO CRD42023392097). Results: From 8,600 records identified, 103 studies were included, with 49,660 positive samples of S. pneumoniae for AMR analysis processed. Most studies were from Brazil (29.1%) and Argentina (18.4%), were cross-sectional (57.3%), reported data on AMR from IPD cases (52.4%), and were classified as moderate risk of bias (50.5%). Resistance to penicillin was 21.7% (95%IC 18.7-25.0, I2: 95.9), and for ceftriaxone/cefotaxime it was 4.7% (95%IC 3.2-6.9, I2: 96.1). The highest resistance for both penicillin and ceftriaxone/cefotaxime was in the age group of 0 to 5 years (32.1% [95%IC 28.2-36.4, I2: 87.7], and 9.7% [95%IC 5.9-15.6, I2: 96.9] respectively). The most frequent serotypes associated with resistance were 14 for penicillin and 19A for ceftriaxone/cefotaxime. Conclusion: Approximately one-quarter of invasive pneumococcal disease isolates in Latin America and the Caribbean displayed penicillin resistance, with higher rates in young children. Ongoing surveillance is essential to monitor serotype evolution and antimicrobial resistance patterns following pneumococcal conjugate vaccine introduction.