RESUMO
A meningite bacteriana é uma inflamação das leptomeninges que envolvem o Sistema Nervoso Central. Essa patologia, que possui diversos agentes etiológicos, apresenta-se na forma de síndrome, com quadro clínico grave. Entre as principais bactérias que causam a meningite, estão a Neisseria meningitis e Streptococcus pneumoniae. A transmissão ocorre através das vias aéreas por meio de gotículas, sendo a corrente sanguínea a principal rota para as bactérias chegarem à barreira hematoencefálica e, a partir dessa, até as meninges. Atualmente existem vários métodos de diagnóstico precisos, onde a cultura de líquido cefalorraquidiano (LCR) é o método padrão ouro. Ademais, a melhora na qualidade do tratamento com beta-lactâmicos e a maior possibilidade de prevenção, devido à elevação do número e da eficácia de vacinas, vem contribuindo para redução dos casos da doença e de sua gravidade. Porém, apesar desses avanços, ainda há um elevado número de mortalidades e sequelas causadas por essa síndrome.
Bacterial meningitis is an inflammation of the leptomeninges that surround the Central Nervous System. This pathology, which has several etiological agents, is presented as a syndrome with a severe clinical scenario. The main bacteria causing meningitis include Neisseria meningitis and Streptococcus pneumoniae. It can be transmitted by droplets through the airways, with the bacteria using the bloodstream as the main route to reach the blood-brain barrier, and from there to the meninges. There are currently several accurate diagnostic methods, with CSF culture being the gold standard. In addition, the improvement in the quality of beta-lactam treatment and the greater possibility of prevention due to the increased number and effectiveness of vaccines have contributed to reducing the number of cases and severity of the disease. Nevertheless, despite these advances, this syndrome still presents a high number of mortalities and sequelae.
Assuntos
Gravidez , Pré-Escolar , Criança , Idoso , Líquido Cefalorraquidiano , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/terapia , Streptococcus pneumoniae/patogenicidade , Síndrome , Bactérias/classificação , Meningites Bacterianas/tratamento farmacológico , beta-Lactamas/uso terapêutico , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Meningite Pneumocócica/tratamento farmacológico , Neisseria/patogenicidadeRESUMO
The virus-bacterial synergism implicated in secondary bacterial infections caused by Streptococcus pneumoniae following infection with epidemic or pandemic influenza A virus (IAV) is well documented. However, the molecular mechanisms behind such synergism remain largely ill-defined. In pneumocytes infected with influenza A virus, subsequent infection with S. pneumoniae leads to enhanced pneumococcal intracellular survival. The pneumococcal two-component system SirRH appears essential for such enhanced survival. Through comparative transcriptomic analysis between the ΔsirR and wt strains, a list of 179 differentially expressed genes was defined. Among those, the clpL protein chaperone gene and the psaB Mn+2 transporter gene, which are involved in the stress response, are important in enhancing S. pneumoniae survival in influenza-infected cells. The ΔsirR, ΔclpL and ΔpsaB deletion mutants display increased susceptibility to acidic and oxidative stress and no enhancement of intracellular survival in IAV-infected pneumocyte cells. These results suggest that the SirRH two-component system senses IAV-induced stress conditions and controls adaptive responses that allow survival of S. pneumoniae in IAV-infected pneumocytes.
Assuntos
Proteínas de Bactérias/metabolismo , Coinfecção/mortalidade , Vírus da Influenza A/patogenicidade , Influenza Humana/mortalidade , Pulmão/patologia , Infecções Pneumocócicas/mortalidade , Streptococcus pneumoniae/patogenicidade , Proteínas de Bactérias/genética , Sobrevivência Celular , Coinfecção/epidemiologia , Humanos , Influenza Humana/microbiologia , Influenza Humana/patologia , Influenza Humana/virologia , Pulmão/microbiologia , Pulmão/virologia , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/patologia , Infecções Pneumocócicas/virologia , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Streptococcus pneumoniae/metabolismo , Estresse Fisiológico , VirulênciaRESUMO
Acute encephalitis is an important cause of mortality and morbidity in children. We retrospectively identified children (≤15 years of age) admitted with suspected encephalitis at the Intensive Care Unit of the Pediatric Department of Cayenne Hospital between January 2007 and December 2018. A total of 30 children with acute encephalitis were identified. The incidence rate varied from 0 to 10.40 cases/100000 children under 15 years. Proven encephalitis was diagnosed in 73% of patients. Nine cases of acute disseminated encephalomyelitis were diagnosed. The causes of infection (44%) were Haemophilus influenzae, followed by Cryptococcus spp and Varicella Zoster Virus. Four children (13%) died: one case of Streptococcus pneumoniae, one of Haemophilus influenzae, one of Mycobacterium tuberculosis and one with no identified cause. Seventeen percent of children had moderate to severe neurological sequelae. The only factor associated with poor outcome was young age at the time of hospitalization (p = 0.03). Conclusion: This study highlights both vaccine-preventable pathogens and acute disseminated encephalomyelitis as the leading causes of childhood encephalitis in French Guiana.
Assuntos
Encefalite/epidemiologia , Encefalite/etiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Cryptococcus/patogenicidade , Encefalite/diagnóstico , Encefalite/microbiologia , Encefalomielite Aguda Disseminada/complicações , Encefalomielite Aguda Disseminada/diagnóstico , Encefalomielite Aguda Disseminada/epidemiologia , Guiana Francesa/epidemiologia , Haemophilus influenzae/patogenicidade , Herpesvirus Humano 3/patogenicidade , Hospitalização , Humanos , Lactente , Unidades de Terapia Intensiva , Mycobacterium tuberculosis/patogenicidade , Prognóstico , Estudos Retrospectivos , Streptococcus pneumoniae/patogenicidadeRESUMO
BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) has been commercially available in Brazil since 2010. We investigated the carriage prevalence, capsular types, and antimicrobial resistance among pneumococci isolated from children immunized with PCV13 in Brazil. METHODS: We analyzed 500 childrenâ¯<â¯6â¯years old attending public (nâ¯=â¯270) and private (nâ¯=â¯230) clinics in Niterói/RJ, Brazil, in 2014. We determined the antimicrobial susceptibility and capsular types for all isolates. RESULTS: Thirty-eight (7.6%) of 500 children had received at least one PCV13 dose. Since only two (0.7%) of 270 children at the public clinic were vaccinated with PCV13, major analyses focused on 36 (15.7%) of 230 children attending private clinics. Nine (25%) of 36 children were pneumococcal carriers. Characteristics associated with carriage were ageâ¯≥â¯2â¯years, cough/expectoration, and childcare center attendance (pâ¯≤â¯0.01). The capsular types found were 15B/C (nâ¯=â¯2), 6C, 11A/D, 16F, 23A, and 23F. Two isolates were non-typeable (NT). Three (33.3%) isolates were multidrug resistant. We found four (44.4%) penicillin non-susceptible pneumococci, with penicillin and ceftriaxone MICs ranging from 0.12 to 4.0⯵g/ml and 0.023-0.5⯵g/ml, respectively. We also detected two (22.2%) erythromycin-resistant isolates (MICs of 3.0 and 256⯵g/ml). CONCLUSIONS: Colonization with PCV13 serotype was rare among the vaccinated children. Increasing PCV13 coverage might help reduce the frequency of major serotypes currently associated with invasive pneumococcal diseases in Brazil, such as 3 and 19A. The isolation of multidrug-resistant serotype 6C and NT isolates in carriage, however, requires close monitoring.
Assuntos
Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Streptococcus pneumoniae/patogenicidade , Brasil , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Infecções Pneumocócicas/imunologia , Sorogrupo , Streptococcus pneumoniae/imunologia , Vacinas Conjugadas/uso terapêuticoRESUMO
Brazil introduced the 10-valent pneumococcal vaccine (PCV10) to the routine national immunization program (NIP) in March 2010. In 2017, we investigated the effects of PCV10 on nasopharyngeal carriage of vaccine-types (VT) and non-vaccine-types (NVT) of Streptococcus pneumoniae (Spn) among children living in São Paulo city. We also compared the prevalence of VT and NVT with previous carriage surveys performed in 2010 (baseline) and 2013. METHOD: The carriage survey was conducted among 531 children, aged 12â¯months to <24â¯months, recruited from public Primary Health Units during the immunization campaign, using previous surveys methodology, except for qPCR, which was performed in the 2017 survey only. RESULTS: No statistical difference was found in the prevalence of Spn either by culture (59.7%) or by qPCR (61.2%). Spn carriage increased from 40.3% (baseline) to 59.7% (2017 survey) (pâ¯<â¯0.001). Colonization by VT isolates significantly decreased by 90.9% (19.8-1.8%) and 95.5% (19.8-0.9%) in the 2013 and 2017 surveys, respectively, compared to that at baseline. NVT isolates increased significantly by 128% (19.6-44.8%) and 185% (19.6-55.9%) in the respective post-PCV10 surveys, most led to high prevalence of serotypes 6C (27%), 15B (9.8%), 19A (9.2%), 15A (6.0%), and 16F (5.7%). In 2017, reduction in serotype 6A (4.2-0.6%, pâ¯<â¯0.001) and increase in serotype 19A (1.8-6.0%, pâ¯=â¯0.001) were found; serotype 3 isolate was not detected in the present survey. We identified the emergence of 19A isolates CC320, associated with high penicillin (MICâ¯≥â¯2.0â¯mg/L) and cefotaxime (MICâ¯≥â¯1.0â¯mg/L) values. CONCLUSION: After 7â¯years of PCV10 introduction in the NIP, colonization by VT among toddlers decreased substantially to a residual level, along with substantial serotype replacement by novel serotypes not present in any current conjugated pneumococcal vaccine and serotype 19A. The present findings can assist policy decisions in Brazil.
Assuntos
Nasofaringe/microbiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Streptococcus pneumoniae/patogenicidade , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Prevalência , Sorogrupo , Streptococcus pneumoniae/imunologia , Vacinas Conjugadas/uso terapêuticoRESUMO
The aim of our study was to describe the clinical features, the etiologies, and the factors associated with poor outcome of encephalitis in French Guiana. Our study was retrospective, including all cases of encephalitis hospitalized in the Cayenne General Hospital, from January 2007 to July 2017. Patients were included through the 2013 encephalitis consortium criteria and the outcome was evaluated using the Glasgow outcome scale at 3 months from the diagnosis of encephalitis. We included 108 patients, giving an approximate incidence rate of four cases/100,000 inhabitants/year. The origin of the encephalitis was diagnosed in 81 cases (75%), and 72 of them (66.7%) were from an infectious origin. The most common infectious causes were Cryptococcus sp. (18.5%) independently of the immune status, Toxoplasma gondii (13.9%), and Streptococcus pneumoniae (5.5%). In the follow-up, 48 patients (46.6%) had poor outcome. Independent risk factors associated with poor outcome at 3 months were "coming from inside area of the region" (P = 0.036, odds ratio [OR] = 4.19; CI 95% = 1.09-16.06), need for mechanical ventilation (P = 0.002, OR = 5.92; CI 95% = 1.95-17.95), and age ≥ 65 years (P = 0.049, OR = 3.99; CI 95% = 1.01-15.89). The most identified cause of encephalitis in French Guiana was Cryptococcus. The shape of the local epidemiology highlights the original infectious situation with some local specific pathogens.
Assuntos
Criptococose/epidemiologia , Encefalite/epidemiologia , Meningoencefalite/epidemiologia , Infecções Pneumocócicas/epidemiologia , Toxoplasmose/epidemiologia , Adolescente , Adulto , Criptococose/microbiologia , Criptococose/mortalidade , Cryptococcus/isolamento & purificação , Cryptococcus/patogenicidade , Encefalite/microbiologia , Encefalite/mortalidade , Encefalite/parasitologia , Feminino , Guiana Francesa/epidemiologia , Escala de Resultado de Glasgow , Humanos , Incidência , Masculino , Meningoencefalite/microbiologia , Meningoencefalite/mortalidade , Meningoencefalite/parasitologia , Pessoa de Meia-Idade , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/mortalidade , Respiração Artificial , Estudos Retrospectivos , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/patogenicidade , Análise de Sobrevida , Toxoplasma/isolamento & purificação , Toxoplasma/patogenicidade , Toxoplasmose/mortalidade , Toxoplasmose/parasitologiaRESUMO
BACKGROUND: This systematic review aims to describe the prevalence, trends, and antibiotic resistance of Streptococcus pneumoniae serotype 19A (Spn19A) that causes invasive and non-invasive diseases in children <5â¯years in Latin-American and Caribbean countries. METHODS: We searched for published (between January 2010 and February 2016) observational and clinical studies within the region including effectiveness and impact on Spn19A after pneumococcal conjugate vaccine (PCV) introduction. We calculated prevalence estimates by country and standardized the frequency of isolates to conduct an interrupted time series analysis for selected countries and to assess the potential changes in disease trends, overall and for Spn19A. RESULTS: We identified and reviewed full-text of 89 publications and included 59 in the analysis. Data from the laboratory surveillance network, SIREVA, were included in 43 (74%) of the invasive pneumococcal disease reports. There are differences in the sensitivity, representativeness, and heterogeneity of laboratory surveillance. There has been and overall reduction in the trend and number of invasive S. pneumoniae isolates in children <5â¯years after PCVs introduction. To date, the prevalence of Spn19A has increased, however, there has been no observed change in the trend. CONCLUSIONS: This updated systematic review provides evidence of a reduction in the total number of invasive pneumococcal disease isolates after the introduction of PCVs in the region but cannot yet conclude a change in the trend of Spn19A disease.
Assuntos
Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Streptococcus pneumoniae/patogenicidade , Vacinas Conjugadas/uso terapêutico , Região do Caribe , Humanos , América Latina , Penicilinas/farmacologia , Infecções Pneumocócicas/tratamento farmacológico , Sorogrupo , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/imunologiaRESUMO
BACKGROUND: In March 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine immunization program in Brazil. We describe the pneumococcal serotypes that caused invasive pneumococcal diseases (IPD) before and after the introduction of PCV10 using data from a national laboratory-based surveillance system. METHOD: We compared the prevalence of vaccine types (VT) and non-vaccine types (NVT) of Streptococcus pneumoniae in three periods, pre-PCV10 (January/2005-December/2009), early post-PCV10 (January/2010-December/2013), and late post-PCV10 (January/2014-December/2015), by episode in meningitis and non-meningitis cases and by age group. Changes in serotype prevalence in the early and late post-PCV10 periods were determined using pre-PCV10 period as a reference. RESULTS: A total of 8971 IPD isolates from patients aged 2â¯months to 99â¯years were analyzed. In the late post-PCV10 period, the VT-IPD reduction in the 2-month to 4-year age group was 83.4% for meningitis and 87.4% for non-meningitis cases; in the age groups 5-17â¯years, 18-64â¯years, and ≥65â¯years, VT declined by 56.1%, 54.1%, and 47.4%, respectively, in meningitis cases, and by 60.9%, 47.7%, and 53.4%, respectively, in non-meningitis cases. NVT-IPD increased throughout the study period, driven mainly by serotypes 3, 6C, and 19A, which remained the predominant types causing IPD in the late post-PCV10 period. CONCLUSION: We observed direct and indirect PCV10 protection against IPD caused by VT and a shift in the distribution of serotypes 5â¯years after the introduction of PCV10. Continued IPD surveillance is needed to evaluate the sustainability of the high prevalence of serotypes 3, 6C, and 19A, which were not included in PCV10.
Assuntos
Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/uso terapêutico , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/patogenicidade , Adolescente , Adulto , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Programas de Imunização , Lactente , Masculino , Meningite Pneumocócica/epidemiologia , Meningite Pneumocócica/microbiologia , Meningite Pneumocócica/prevenção & controle , Pessoa de Meia-Idade , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Prevalência , SorogrupoRESUMO
BACKGROUND: In recent years, the idea of a highly immunogenic protein-based vaccine to combat Streptococcus pneumoniae and its severe invasive infectious diseases has gained considerable interest. However, the target proteins to be included in a vaccine formulation have to accomplish several genetic and immunological characteristics, (such as conservation, distribution, immunogenicity and protective effect), in order to ensure its suitability and effectiveness. This study aimed to get comprehensive insights into the genomic organization, population distribution and genetic conservation of all pneumococcal surface-exposed proteins, genetic regulators and other virulence factors, whose important function and role in pathogenesis has been demonstrated or hypothesized. RESULTS: After retrieving the complete set of DNA and protein sequences reported in the databases GenBank, KEGG, VFDB, P2CS and Uniprot for pneumococcal strains whose genomes have been fully sequenced and annotated, a comprehensive bioinformatic analysis and systematic comparison has been performed for each virulence factor, stand-alone regulator and two-component regulatory system (TCS) encoded in the pan-genome of S. pneumoniae. A total of 25 S. pneumoniae strains, representing different pneumococcal phylogenetic lineages and serotypes, were considered. A set of 92 different genes and proteins were identified, classified and studied to construct a pan-genomic variability map (variome) for S. pneumoniae. Both, pneumococcal virulence factors and regulatory genes, were well-distributed in the pneumococcal genome and exhibited a conserved feature of genome organization, where replication and transcription are co-oriented. The analysis of the population distribution for each gene and protein showed that 49 of them are part of the core genome in pneumococci, while 43 belong to the accessory-genome. Estimating the genetic variability revealed that pneumolysin, enolase and Usp45 (SP_2216 in S. p. TIGR4) are the pneumococcal virulence factors with the highest conservation, while TCS08, TCS05, and TCS02 represent the most conserved pneumococcal genetic regulators. CONCLUSIONS: The results identified well-distributed and highly conserved pneumococcal virulence factors as well as regulators, representing promising candidates for a new generation of serotype-independent protein-based vaccine(s) to combat pneumococcal infections.
Assuntos
Variação Genética , Streptococcus pneumoniae/genética , Fatores de Virulência/genética , Proteínas de Bactérias/genética , Mapeamento Cromossômico , Genes Bacterianos , Genes Reguladores , Genoma Bacteriano , Filogenia , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/patogenicidadeRESUMO
Introducción: Las meningitis bacterianas en niños son causa de importante morbimortalidad. Los principales agentes etiológicos son Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae. En los últimos años, luego de la introducción sucesiva de vacunas conjugadas al calendario nacional de inmunizaciones, se ha visto un cambio en la epidemiología de estas infecciones. Objetivo: Describir las características clínicas, epidemiológicas y evolutivas de los niños hospitalizados con meningitis bacteriana confirmada microbiológicamente entre 2011 y 2016 en un hospital de tercer nivel de complejidad. Materiales y métodos: Cohorte retrospectiva. Se incluyeron niños entre 1 mes de vida y 17 años con cuadro clínico compatible con meningitis bacteriana y cultivo positivo y/o PCR en líquido cefalorraquídeo y/o hemocultivos positivos para Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae b. Se registraron las características demográficas, clínicas y evolutivas hasta los 30 días del egreso. Se utilizó mediana y rango intercuartilo (RIC) para variables continuas y porcentaje para variables categóricas. Se utilizó Stata 10. Resultados: n=65. Edad: mediana de 9 meses (RIC 4-35). Varones: 58% (n=38). Se identificó Neisseria meningitidis en un 48% (n=31), Haemophilus influenzae b en un 26% (n=17) y Streptococcus pneumoniae en un 26% (n=17). El 26% (n=17) de los pacientes presentaba alguna comorbilidad. Tuvieron hemocultivos positivos el 62% (n = 40) de los pacientes y 86% (n=55) de los líquidos cefalorraquídeos. Todos los pacientes recibieron tratamiento antimicrobiano con ceftriaxona tanto como tratamiento empírico como definitivo y 92% (n=60) recibieron corticoides empíricos. La mediana de días de internación fue de 11 (RIC 8-17). El 28% (n=18) requirió cuidados intensivos, y el 8% (n=5) falleció. Durante el período de estudio se observó que la frecuencia de meningitis por Streptococcus pneumoniae disminuyó en el final del estudio (9% en 2016 vs 60% en 2011), mientras que la frecuencia de meningitis por Neisseria meningitidis en 2016 fue mayor que al inicio del período (64% en 2016 vs. 40% en 2011). La frecuencia de identificación de Haemophilus influenzae b se mantuvo estable. Conclusiones: Las meningitis bacterianas confirmadas por Neisseria meningitidis, Streptococcus pneumoniae y Haemophilus influenzae b prevalecieron en niños menores de 12 meses. En esta cohorte se observó un predominio de las infecciones por Neisseria meningitidis en los últimos años, y una disminución en la frecuencia de meningitis por Streptococcus pneumoniae en el período post introducción de la vacuna conjugada 13 valente al calendario nacional de inmunizaciones. (AU)
Introduction: In children, bacterial meningitis is an important cause of morbidity and mortality. The main etiological agents are Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. Over the last years, the successive introduction of conjugated vaccines in the national immunization calendar has led to a change in the epidemiology of these infections. Objective: To describe the clinical and epidemiological features and outcome of children admitted because of microbiologically confirmed meningitis seen between 2011 and 2016 at a tertiary care hospital. Material and methods: A retrospective cohort study was conducted. Children between 1 month of life and 17 years of age with clinical features compatible with bacterial meningitis and positive cultures and/or PCR in cerebrospinal fluid (CSF) and/or positive blood cultures for Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae b were included. Demographic, clinical, and outcome features were recorded until 30 days after discharge. Median and interquartile range (IQR) were calculated for continuous variables and percentages for categorical variables. The Stata 10 program was used. Results: n=65. Age: median was 9 months (IQR 4-35). Boys: 58% (n=38). Neisseria meningitidis was identified in 48% (n=31), Haemophilus influenzae b in 26% (n=17), and Streptococcus pneumoniae in 26% (n=17). Overall, 26% (n=17) of the patients presented with comorbidities. Positive blood cultures were found in 62% (n = 40) and positive CSF cultures in 86% (n=55) of the patients. All patients received antimicrobial treatment with ceftriaxone both empirically and as final treatment and corticosteroids were empirically started in 92% (n=60). Median hospital stay was 11 days (IQR 8-17). Overall, 28% (n=18) required intensive care and 8% (n=5) of the patients died. The incidence of meningitis due to Streptococcus pneumoniae was observed to diminish at the end of the study period (9% in 2016 vs 60% in 2011), while the incidence of meningitis due to Neisseria meningitidis in 2016 was higher than at the end of the study period (64% in 2016 vs. 40% in 2011). The frequency of identification of Haemophilus influenzae b remained stable. Conclusions: Confirmed bacterial infections due to Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae b were prevalent in infants younger than 12 months of age in this cohort of patients. Infections due to Neisseria meningitidis predominated over the last years and the incidence of meningitis due to Streptococcus pneumoniae diminished after the introduction of the 13 valent conjugated vaccine was introduced in the national immunization calendar.(AU)