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Streptococcus pneumoniae is a major pathogen responsible for severe complications in patients with prior influenza A virus (IAV) infection. We have previously demonstrated that S. pneumoniae exhibits increased intracellular survival within IAV-infected cells. Fluoroquinolones (FQs) are widely used to treat pneumococcal infections. However, our prior work has shown that S. pneumoniae can develop intracellular FQ persistence, a phenomenon triggered by oxidative stress within host cells. This persistence allows the bacteria to withstand high FQ concentrations. In this study, we show that IAV infection enhances pneumococcal FQ persistence during intracellular survival within pneumocytes, macrophages, and neutrophils. This enhancement is partly due to increased oxidative stress induced by the viral infection. We find that this phenotype is particularly pronounced in autophagy-proficient host cells, potentially resulting from IAV-induced blockage of autophagosome-lysosome fusion. Moreover, we identified several S. pneumoniae genes involved in oxidative stress response that contribute to FQ persistence, including sodA (superoxide dismutase), clpL (chaperone), nrdH (glutaredoxin), and psaB (Mn+2 transporter component). Our findings reveal a novel mechanism of antibiotic persistence promoted by viral infection within host cells. This underscores the importance of considering this phenomenon when using FQs to treat pneumococcal infections, especially in patients with concurrent influenza A infection.

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Purpose of Review: Despite the availability of effective vaccines against the three primary pathogens (Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis) that cause bacterial meningitis, this condition remains a significant cause of morbidity, neurologic sequelae, and mortality among children and adults living in low-income and middle-income countries. Recent Findings: Bacterial meningitis represents a significant public health challenge for national and global health systems. Since vaccine-preventable meningitis remains highly prevalent in low-income and middle-income countries, the World Health Organization (WHO) recently developed a global roadmap to defeating meningitis by 2030 and ameliorating its associated neurological sequelae. Summary: There is a need for a global approach to surveillance and prevention of bacterial meningitis. Increasing vaccination coverage with conjugate vaccines against pneumococcus and meningococcus with optimal immunization schedules are high-value healthcare interventions. Additionally, overcoming diagnostic challenges and the early institution of empirical antibiotic therapy and, when feasible, adjunctive steroid therapy constitutes the pillars of reducing the disease burden of bacterial meningitis in resource-limited settings.

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BACKGROUND: Streptococcus pneumoniae bacteremia may result in Infective Endocarditis (IE). In the pre-antibiotic era, it caused 10 %‒15 % 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, 2005‒2023. 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 (22‒77). 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 Risco

RESUMO

Introduction: Invasive Pneumococcal Disease (IPD) causes significant morbidity and mortality in children under 5 y. Colombia introduced PCV10 vaccination in 2012, and the Neumocolombia network has been monitoring IPD in pediatric patients since 2008. Materials and methods: This study is a secondary analysis of a prospective cohort involving pediatric patients with IPD admitted to 17 hospitals in Colombia, from January 1st, 2017, to December 31st, 2022. We present data on serotypes (Spn), clinical characteristics, and resistance patterns. Results: We report 530 patients, 215 (40.5%) were younger than 24 months. Among these, 344 cases (64.7%) presented with pneumonia, 95 (17.9%) with primary bacteremia, 53 (10%) with meningitis, 6 (1.1%) had pneumonia and meningitis, and 32 (6%) had other IPD diagnosis. The median hospital stay was 12 days (RIQ 8-14 days), and 268 (50.6%) were admitted to the ICU, of whom 60 (11.3%) died. Serotyping was performed in 298 (56.1%). The most frequent serotypes were Spn19A (51.3%), Spn6C (7.7%), Spn3 (6.7%), Spn6A (3.6%), and Spn14 (3.6%). Of 495 (93%) isolates with known susceptibility, 46 (9.2%) were meningeal (M) and 449 (90.7%) non-meningeal (NM). Among M isolates, 41.3% showed resistance to penicillin, and 21.7% decreased susceptibility to ceftriaxone. For NM isolates, 28.2% had decreased susceptibility to penicilin, and 24.2% decreased susceptibility to ceftriaxone. Spn19A showed the highest resistant to penicillin at 47% and was linked to multiresistance. Conclusion: The prevalence of PCV10-included serotypes decreased, while serotypes 19A and 6C increased, with Spn19A being associated with multiresistance. These findings had played a crucial role in the decision made by Colombia to modify its immunization schedule by switching to PCV13 in July 2022.

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INTRODUCTION: In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23; PCV13 → PPSV23) has been recommended for all adults aged ≥ 65 years and younger adults with chronic medical ("moderate-risk") or immunocompromising ("high-risk") conditions since 2017. With the approval of a 20-valent PCV (PCV20), we evaluated the cost-effectiveness of PCV20 versus current recommendations for moderate-/high-risk adults aged 18-64 years and all adults 65-99 years. METHODS: A probabilistic cohort model was used to project lifetime outcomes and costs associated with invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP), and the expected impact of vaccination. Clinical outcomes were projected annually based on Argentinean data. Economic costs were estimated based on cases and corresponding medical costs (adjusted to 2023 USD) and costs of vaccine and administration. Cost-effectiveness of PCV20 was evaluated versus the current strategy, PCV13 → PPSV23, and alternatively, versus sequentially administered 15-valent PCV and PPSV23 (PCV15 → PPSV23), and presented as cost per quality-adjusted life year gained; a healthcare system perspective was used. Costs and benefits were discounted at 3%/year. RESULTS: PCV20 in lieu of PCV13 → PPSV23 among moderate-/high-risk adults aged 18-64 years and all adults 65-99 years (N = 13.4M) prevented 3838 IPD, 4377 inpatient NBP, and 6003 outpatient NBP cases, and 1865 disease-related deaths; relative to PCV15 → PPSV23 the corresponding reductions were 2775, 3285, 4518, and 1348. PCV20 was projected to be the dominant strategy versus PCV13 → PPSV23 and PCV15 → PPSV23 as overall costs were lower by $87.6M and $80.8M, respectively. In probabilistic sensitivity analyses, PCV20 was dominant (i.e., more effective, less costly) in 100% of 1000 simulations. CONCLUSIONS: Analyses suggest implementing a PCV20 vaccination program in moderate-/high-risk adults aged 18-64 years and all adults ≥ 65 years-in lieu of PCV13 → PPSV23-would yield substantial reductions in pneumococcal disease and would be cost saving to the Argentinean healthcare system.

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Pneumococcal pneumonia has a high disease burden in both children and adults. Older adults and those with certain underlying conditions are more susceptible to severe pneumococcal disease resulting in considerable economic burden on the healthcare system. In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) a year later is recommended for all adults aged ≥ 65 years and adults aged 18­64 years with underlying risk conditions. Despite vaccination efforts, prevalence of pneumococcal disease remains high. Two higher-valent PCVs­15-valent PCV (PCV15) and 20-valent PCV (PCV20)­are available for use in adults with PCV20 offering additional serotype coverage. This study assessed the cost-effectiveness of replacing current (PCV13 → PPSV23) and alternative (PCV15 → PPSV23) vaccination strategies with PCV20 alone. The use of PCV20 was evaluated among Argentinean adults aged 18­64 years with underlying risk conditions and all adults aged 65­99 years (N = 13 million). Over a lifetime time horizon, compared to PCV13 → PPSV23, PCV20 use would avert 14,218 cases and 1865 deaths, and increase quality-adjusted life years by 8655. Compared to PCV15 → PPSV23, PCV20 reduced cases and deaths by 10,578 and 1348, respectively, and increased quality-adjusted life years by 6341. In both comparisons, PCV20 use was cost saving with $87.6 million and $80.8 million lower costs compared to PCV13 → PPSV23 and PCV15 → PPSV23, respectively. Results of the cost-effectiveness analyses suggest that the use of PCV20 is a cost-saving strategy, reducing overall costs to the healthcare system and improving public health.

RESUMO

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.

Assuntos

Proteínas de Bactérias , Streptococcus pneumoniae , Humanos , Animais , Camundongos , Proteínas de Bactérias/química , Streptococcus pneumoniae/genética , Vacinas Pneumocócicas/metabolismo , Anticorpos Antibacterianos , Camundongos Endogâmicos BALB C

RESUMO

Bacterial meningitis is still a significant public health concern, with high morbidity and mortality rates. Despite this, it is still a rare event that requires the bacterial invasion of the meninges. However, some predisposing factors can trigger recurrent episodes of meningitis. This study is aimed at determining the clinical characteristics and the molecular epidemiology of episodes of recurrent community-acquired meningitis with and without predisposing factors. For this purpose, we performed a retrospective study of our laboratory database during the period of 2010 to 2020. Additionally, using molecular tools developed in our previous works, the epidemiology of the pathogens causing these episodes was analyzed using cerebrospinal fluid samples, especially in the absence of isolated strains. We observed a total of 1,779 meningitis cases and 230 were caused by Streptococcus pneumoniae. Of those, 16 were recurrent meningitis episodes (16/1,779; 0.9%) from seven patients. Pneumococcus was the main agent responsible in these recurrent episodes and only two episodes were caused by Haemophilus influenzae. The mean age of these patients was 20 years old and three had predisposing factors which could have led to contracting meningitis. The samples presented different pneumococcal serotypes. Most of them were non-vaccine-covered serotypes and antibiotic susceptible strains. Therefore, it was demonstrated how the practical employment of molecular tools, developed for research, when applied in the routine of diagnosis, can provide important information for epidemiological surveillance. Furthermore, it was shown how pneumococcus was the leading cause of recurrent community-acquired meningitis without predisposing factors, suggesting that pneumococcal vaccination may be necessary, even in those groups of individuals considered to be less susceptible.

Assuntos

Infecções Comunitárias Adquiridas , Meningite Pneumocócica , Recidiva , Streptococcus pneumoniae , Humanos , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/epidemiologia , Meningite Pneumocócica/epidemiologia , Meningite Pneumocócica/microbiologia , Adulto , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/classificação , Estudos Retrospectivos , Feminino , Masculino , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Fatores de Risco , Sorogrupo , Antibacterianos , Haemophilus influenzae/genética , Haemophilus influenzae/isolamento & purificação , Haemophilus influenzae/classificação

RESUMO

Background: Streptococcus pneumoniae, a prominent human pathogen linked to various systemic diseases, includes non-typeable pneumococci marked by the absence of a detectable capsule. However, the majority of invasive infections are attributed to encapsulated strains. This case report details the first documented instance of invasive disease caused by non-typeable S. pneumoniae in Argentina since 2017. Case Presentation: A 19-year-old woman presented with haemorrhagic injuries attributed to chronic oral mucosa irritation. Subsequent hospitalization revealed bone marrow aplasia, leading to antibiotic, antifungal, antiviral, and immunosuppressive treatments, culminating in her discharge. Two weeks later, she was readmitted with sepsis related to a respiratory focus, exhibiting a negative COVID-PCR test. After ten days, ICU admission revealed additional infections: positive COVID-PCR test, fungal sinusitis, and S. pneumoniae bacteremia. Targeted treatments led to improvement, and the patient was subsequently discharged. S pneumoniae characterization: Verification of the capsule's absence utilized traditional methods such as the Quellung reaction, transmission electron microscopy, molecular assays, and Whole Genome Sequencing (WGS). The isolate, identified as ST18335, displayed genetic features and antibiotic resistance patterns, concordant between WGS and the agar dilution method. It demonstrated non-susceptibility to penicillin and cefotaxime, based on meningitis breakpoints, as well as meropenem and cotrimoxazole. Conclusion: This case underscores the clinical significance of non-typeable S. pneumoniae, emphasizing the necessity for a comprehensive approach to identification and characterization. The findings contribute to ongoing discussions regarding the challenges posed by non-typeable strains in vaccine development, understanding clinical impacts, and addressing antibiotic resistance. As the pneumococcal epidemiological landscape evolves, this case serves as a valuable addition to the evolving knowledge surrounding non-typeable S. pneumoniae, highlighting the continued need for surveillance and research in infectious diseases.

RESUMO

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 , Adolescente

RESUMO

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/imunologia

RESUMO

Despite the introduction of the pneumococcal vaccine, Streptococcus pneumoniae remains a cause of invasive diseases in Brazil. This study provides the distribution of serotypes and antimicrobial susceptibility patterns for pneumococcal isolates before and during the years of the COVID-19 pandemic in two age groups, <5 and ≥50 years. This is a national laboratory-based surveillance study that uses data from the Brazilian national laboratory for invasive S. pneumoniae from the pre-COVID-19 (January 2016 to January 2020) and COVID-19 (February 2020 to May 2022) periods. Antimicrobial resistance was evaluated by disk diffusion and minimum inhibitory concentration. The year 2020 was marked by a 44.6% reduction in isolates received and was followed by an upward trend from 2021 onwards, which became evident in 2022. No differences were observed in serotypes distribution between the studied periods. The COVID-19 period was marked by the high prevalence of serotypes 19A, 3, and 6C in both age groups. Serotypes 19A and 6C were related to non-antimicrobial susceptibility. We observed a reduction in S. pneumoniae, without changes in serotypes distribution and epidemiological capsular switch during the COVID-19 period. We observed elevated resistance rates, mainly to penicillin and ceftriaxone for non-meningitis cases in children under 5 years of age.

RESUMO

Pneumococcal diseases are an important public health problem, with high mortality rates in young children. Although conjugated pneumococcal vaccines offer high protection against invasive pneumococcal diseases, this is restricted to vaccine serotypes, leading to serotype replacement. Furthermore, the current vaccines do not protect neonates. Therefore, several protein-based pneumococcal vaccines have been studied over the last few decades. Our group established a recombinant BCG expressing rPspA-PdT as a prime/rPspA-PdT boost strategy, which protected adult mice against lethal intranasal pneumococcal challenge. Here, we immunized groups of neonate C57/Bl6 mice (6-10) (at 5 days) with rBCG PspA-PdT and a boost with rPspA-PdT (at 12 days). Controls were saline or each antigen alone. The prime/boost strategy promoted an IgG1 to IgG2c isotype shift compared to protein alone. Furthermore, there was an increase in specific memory cells (T and B lymphocytes) and higher cytokine production (IFN-γ, IL-17, TNF-α, IL-10, and IL-6). Immunization with rBCG PspA-PdT/rPspA-PdT showed 100% protection against pulmonary challenge with the WU2 pneumococcal strain; two doses of rPspA-PdT showed non-significant protection in the neonates. These results demonstrate that a prime/boost strategy using rBCG PspA-PdT/rPspA-PdT is effective in protecting neonates against lethal pneumococcal infection via the induction of strong antibody and cytokine responses.

RESUMO

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 C

RESUMO

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 , Sorogrupo

RESUMO

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.

Assuntos

Antibacterianos , Farmacorresistência Bacteriana , Infecções Pneumocócicas , Streptococcus pneumoniae , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Humanos , Infecções Pneumocócicas/microbiologia , América Latina , Antibacterianos/farmacologia , Pré-Escolar , Vacinas Pneumocócicas , Lactente , Criança , Testes de Sensibilidade Microbiana , Região do Caribe/epidemiologia

RESUMO

We evaluated whether viable and non-viable Lacticaseibacillus rhamnosus CRL1505 (Lr05V or Lr05NV, respectively) was able to improve emergency myelopoiesis induced by Streptococcus pneumoniae (Sp) infection. Adult Swiss-mice were orally treated with Lr05V or Lr05NV during five consecutive days. The Lr05V and Lr05NV groups and untreated control group received an intraperitoneal dose of cyclophosphamide (Cy-150 mg/kg). Then, the mice were nasally challenged with Sp (107 UFC/mice) on day 3 post-Cy injection. After the pneumococcal challenge, the innate and myelopoietic responses were evaluated. The control group showed a high susceptibility to pneumococcal infection, an impaired innate immune response and a decrease of hematopoietic stem cells (HSCs: Lin-Sca-1+c-Kit+), and myeloid multipotent precursors (MMPs: Gr-1+Ly6G+Ly6C-) in bone marrow (BM). However, lactobacilli treatments were able to significantly increase blood neutrophils and peroxidase-positive cells, while improving cytokine production and phagocytic activity of alveolar macrophages. This, in turn, led to an early Sp lung clearance compared to the control group. Furthermore, Lr05V was more effective than Lr05NV to increase growth factors in BM, which allowed an early HSCs and MMPs recovery with respect to the control group. Both Lr05V and Lr05NV were able to improve BM emergency myelopiesis and protection against respiratory pathogens in mice undergoing chemotherapy.

Assuntos

Hospedeiro Imunocomprometido , Lacticaseibacillus rhamnosus , Mielopoese , Probióticos , Streptococcus pneumoniae , Animais , Camundongos , Mielopoese/efeitos dos fármacos , Lacticaseibacillus rhamnosus/imunologia , Probióticos/administração & dosagem , Probióticos/farmacologia , Streptococcus pneumoniae/imunologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/microbiologia , Imunidade Inata , Modelos Animais de Doenças , Citocinas/metabolismo , Ciclofosfamida/farmacologia , Neutrófilos/imunologia , Masculino

RESUMO

BACKGROUND: In 2010, Brazil introduced the ten-valent pneumococcal conjugate vaccine (PCV10) in the national infant immunization program. Limited data on the long-term impact of PCV10 are available from lower-middle-income settings. We examined invasive pneumococcal disease (IPD) in Salvador, Bahia, over 11 years. METHODS: Prospective laboratory-based surveillance for IPD was carried out in 9 hospitals in the metropolitan region of Salvador from 2008 to 2018. IPD was defined as Streptococcus pneumoniae cultured from a normally sterile site. Serotype was determined by multiplex polymerase chain reaction and/or Quellung reaction. Incidence rates per 100,000 inhabitants were calculated for overall, vaccine-type, and non-vaccine-type IPD using census data as the denominator. Incidence rate ratios (IRRs) were calculated to compare rates during the early (2010-2012), intermediate (2013-2015), and late (2016-2018) post-PCV10 periods in comparison to the pre-PCV10 period (2008-2009). RESULTS: Pre-PCV10, overall IPD incidence among all ages was 2.48/100,000. After PCV10 introduction, incidence initially increased (early post-PCV10 IRR 3.80, 95% CI 1.18-1.99) and then declined to 0.38/100,000 late post-PCV10 (IRR 0.15; 95% CI 0.09-0.26). The greatest reductions in the late post-PCV10 period were observed in children aged ≤2 years, with no cases (IRR not calculated) and those ≥60 years (IRR 0.11, 95% CI 0.03-0.48). Late post-PCV10, significant reductions were observed for both PCV10 serotypes (IRR 0.02; 95% CI 0.0-0.15) and non-PCV10 serotypes (IRR 0.27; 95%CI 0.14-0.53). Non-PCV10 serotypes 15B, 12F, 3, 17F, and 19A became predominant late post-PCV10 without a significant increase in serotype-specific IPD incidence compared to pre-PCV10. CONCLUSION: Significant declines in IPD, including among adults not eligible for vaccination, suggest direct and indirect protection up to nine years after PCV10 introduction, without evidence of significant replacement disease. Continued surveillance is needed to monitor changes in non-vaccine serotypes and inform decisions about introducing higher valent PCVs.

Assuntos

Infecções Pneumocócicas , Lactente , Criança , Adulto , Humanos , Brasil/epidemiologia , Estudos Prospectivos , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Sorogrupo , Incidência , Vacinas Conjugadas

RESUMO

Streptococcus pneumoniae causes serious illnesses, such as pneumonia, bacteremia, and meningitis, mainly in immunocompromised individuals and those of extreme ages. Currently, pneumococcal conjugate vaccines (PCVs) are the best allies against pneumococcal diseases. In Brazil, the 10-valent and 13-valent PCVs have been available since 2010, but the threat of antimicrobial resistance persists and has been changing over time. We conducted a systematic review of the literature with works published since 2000, generating a parallel between susceptibility data on isolates recovered from colonization and invasive diseases before and after the implementation of PCVs for routine childhood use in Brazil. This systematic review was based on the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Literature Reviews and Meta-Analyses (PRISMA) guidelines. Despite the inclusion of PCVs at a large scale in the national territory, high frequencies of non-susceptibility to important drugs used in pneumococcal diseases are still observed, especially penicillin, as well as increasing resistance to macrolides. However, there are still drugs for which pneumococci have a comprehensive sensitivity profile.

RESUMO

BACKGROUND: The Pneumococcal conjugate vaccine (PCV) has decreased cases of invasive pneumococcal disease (IPD) worldwide. However, the impact of PCVs introduction may be affected by the serotype distribution in a specific context. METHODS: Cross-sectional multicenter passive surveillance study of IPD cases in pediatric patients hospitalized in Lima, Peru between 2016 and 2019 (after PCV13 introduction) to determine the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae. Serotyping was performed by a sequential multiplex PCR and confirmed by whole genome sequencing. RESULTS: Eighty-five S. pneumoniae isolates were recovered (4.07/100,000 among children <60 months of age). Serotype 19A was the most common (49.4%). Children infected with serotype 19A in comparison with children infected with other serotypes were younger, had a lower rate of meningitis and higher rates of pneumonia, complicated pneumonia and antimicrobial resistance; 28.6% of patients with serotype 19A have received at least one dose of PCV13 vs. 62.8% of patients with other serotypes. Using MIC-breakpoints, 81.2% (56/69) of non-meningitis strains and 31.2% (5/16) of meningitis strains were susceptible to penicillin; 18.8% (3/16) of meningitis strains had intermediate resistance to ceftriaxone. Resistance to azithromycin was 78.8% (67/85). Serotype 19A frequency increased over time in the same study population, from 4.2% (4/96) in 2006-2008, to 8.6% (5/58) in 2009-2011, to 49.4% (42/85) in the current study (2016-2019) (p < 0.001). CONCLUSIONS: After PCV13 introduction in Peru, serotype 19A remains the most prevalent; however, the vaccination coverage is still not optimal. Therefore, additonal surveillance studies are needed to determine the remaining IPD burden.

Assuntos

Anti-Infecciosos , Meningite , Infecções Pneumocócicas , Pneumonia , Criança , Humanos , Lactente , Streptococcus pneumoniae , Sorogrupo , Vacinas Conjugadas , Criança Hospitalizada , Peru/epidemiologia , Estudos Transversais , Vacinas Pneumocócicas , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Sorotipagem

RESUMO

Otitis media with effusion (OME) is a type of otitis media (OM) characterized by the presence of fluid behind intact tympanic membrane and is one of the most common diseases of early childhood. It is an infectious disease associated with the presence of many pathogenic bacteria in the middle ear of affected individuals. This study was aimed to determine the prevalence of Gram-positive bacteria from the middle ear of OME patients in the population of Southern Punjab, Pakistan. The incidence of OME under comprehensive healthcare setting was investigated in patients who consulted at the department of ear, throat and nose, Bahawal Victoria Hospital (BVH), Bahawalpur, from December, 2019 to May, 2021. Ear swabs were taken from affected and normal individuals. After culturing bacteria from the ear swabs, microscopic analysis and biochemical tests were performed to characterize the cultured Gram-positive bacteria. Out of 352 patients examined, 109 (30.9%) patients had OME. Age of the participants ranged from 14 to 50 years; individuals between the ages of 14 and 22 years had the highest infection rates, while individuals between 40 and 50 years had the lowest rate of infection. Tympanic membrane perforation, fever, cough, sore throat, ear pain and hearing problem showed association with symptoms of OME. Microscopic analysis and biochemical characterization showed the presence of streptococci and staphylococci in all the studied samples. The most frequently isolated bacteria were Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus with percentage of 53.3%, 20% and 13.3% respectively. Enterococcus faecalis (6.6%) and Staphylococcus epidermidis (6.6%) were also identified in the studied samples. This study will help in the better medical administration of OME affected individuals.

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A otite média com efusão (OME) é um tipo de otite média (OM) caracterizada pela presença de líquido atrás da membrana timpânica intacta e é uma das doenças mais comuns durante a primeira infância. Trata-se de uma doença infecciosa associada à presença de muitas bactérias patogênicas na orelha média dos indivíduos afetados. Este estudo teve como objetivo determinar a prevalência de bactérias Gram-positivas do ouvido médio de pacientes com OME na população do sul de Punjab, Paquistão. A incidência de OME em ambiente de saúde abrangente foi investigada em pacientes que consultaram no departamento de ouvido, garganta e nariz, Hospital Bahawal Victoria (BVH), Bahawalpur, de dezembro de 2019 a maio de 2021. Cotonetes de orelha foram coletados de indivíduos afetados e normais. Após a cultura das bactérias dos swabs auriculares, análises microscópicas e testes bioquímicos foram realizados para caracterizar as bactérias Gram-positivas cultivadas. Dos 352 pacientes examinados, 109 (30,9%) apresentavam OME. A idade dos participantes variou de 14 a 50 anos; indivíduos entre 14 e 22 anos apresentaram as maiores taxas de infecção, enquanto indivíduos entre 40 e 50 anos apresentaram as menores taxas de infecção. Perfuração da membrana timpânica, febre, tosse, dor de garganta, dor de ouvido e problema de audição apresentaram associação com sintomas de OME. A análise microscópica e a caracterização bioquímica mostraram a presença de estreptococos e estafilococos em todas as amostras estudadas. As bactérias isoladas com maior frequência foram Streptococcus pneumoniae, Streptococcus pyogenes e Staphylococcus aureus com percentuais de 53,3%, 20% e 13,3%, respectivamente. Enterococcus faecalis (6,6%) e Staphylococcus epidermidis (6,6%) também foram identificados nas amostras estudadas. Este estudo ajudará na melhor administração médica de indivíduos afetados por OME.

Assuntos

Humanos , Otite Média , Streptococcus pneumoniae , Membrana Timpânica/anormalidades , Povos Indígenas , Bactérias Gram-Positivas , Paquistão