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1.
Vaccine ; 39(2): 431-437, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33243632

RESUMO

BACKGROUND: In 2011, the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced by the 10-valent vaccine (PCV10) in the Netherlands. We report on impact and effectiveness against invasive pneumococcal disease (IPD) in children aged under 5 years by switching from PCV7 to PCV10. METHOD: We included IPD cases between 2004 and 2019 in children aged < 5 years reported via the national surveillance system. To assess the impact of the PCV10 vaccination program we compared IPD incidence 6-8 years after PCV10 introduction (2017-2019) to the two years just before the switch to PCV10 (2009-2011). We estimated vaccine effectiveness (VE) using the indirect cohort method, comparing vaccination status (at least two vaccine doses) in IPD-cases caused by PCV10 serotypes (cases) to non-PCV10 IPD cases (controls), in children eligible for PCV10. RESULTS: The overall incidence decreased from 8.7 (n = 162) in 2009-2011 to 7.3 per 100.000 (n = 127) in 2017-2019 (Incidence rate ratio (IRR) 0.83, 95%CI: 0.66; 1.05). IPD caused by the additional serotypes included in PCV10 declined by 93% (IRR 0.07, 95%CI: 0.02; 0.23). Incidence of non-PCV10 IPD showed a non-significant increase (IRR 1.25, 95%CI: 0.96; 1.63). Among 231 IPD-cases eligible for PCV10, the overall VE was 91% (95%CI: 67; 97) and did not differ by sex or age at diagnosis. Effectiveness against non-PCV10 serotype 19A IPD was non-significant with an estimate of 28% (95%CI:-179; 81). CONCLUSION: PCV10 is highly effective in protecting against IPD in Dutch children under 5 years with limited serotype replacement after switching from PCV7 to PCV10. We found no evidence for significant cross-protection of PCV10 against 19A serotype IPD.


Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Criança , Pré-Escolar , Humanos , Incidência , Lactente , Países Baixos/epidemiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Vacinas Conjugadas
2.
Vaccine ; 38(49): 7850-7857, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33097311

RESUMO

Neisseria meningitidis serogroup B is a major cause of invasive meningococcal disease in Europe. In the absence of a conjugate serogroup B vaccine, a subcapsular 4CMenB vaccine was developed. Data on 4CMenB vaccine efficacy is still limited. Recently, genomic MATS (Meningococcal Antigen Typing System) was developed as a tool to predict strain coverage, using vaccine antigens sequence data. We characterized all invasive meningococcal isolates received by the Netherlands Reference Laboratory for Bacterial Meningitis (NRLBM) in two epidemiological years 2017-2019 using whole-genome sequencing and determined serogroup, clonal complex (cc) and estimated 4CMenB vaccine coverage by gMATS. Of 396 cases of invasive meningococcal disease, corresponding to an incidence of 1.22 cases/105 inhabitants, 180 (45%) were serogroup W, 155 (39%) serogroup B, 46 (12%) serogroup Y, 10 (3%) serogroup C, 2 non-groupable (0.5%) and 3 (0.7%) unknown. The incidence was the highest among 0-4 years olds (4 cases/105 inhabitants), and 57/72 (79%) of these cases were serogroup B. Serogroup W predominated among persons 45 years of age or older with 110/187 (59%) cases. Serogroup B isolates comprised 11 different clonal complexes, with 103/122 (84%) isolates belonging to 4 clonal complexes: cc32, cc41/44, cc269 and cc213. In contrast, serogroup W isolates were genetically similar with 95% belonging to cc11. Of 122 serogroup B isolates, 89 (73%; 95% CI: 64-80%) were estimated to be covered by 4CMenB and the degree of coverage varied largely by clonal complex and age. Among the 0-4 year olds, 25 of 43 (58%; 95% CI: 43-72%) MenB isolates were estimated to be covered. Since the coverage of the 4CMenB vaccine is dependent on circulating clonal complexes, our findings emphasize the need for surveillance of circulating meningococcal strains. In addition, estimation of age specific coverage is relevant to determine the right target age group for vaccination.


Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis Sorogrupo B , Antígenos de Bactérias , Pré-Escolar , Europa (Continente) , Humanos , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Neisseria meningitidis Sorogrupo B/genética , Países Baixos/epidemiologia
3.
Clin Microbiol Infect ; 26(4): 513.e7-513.e11, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31525519

RESUMO

OBJECTIVE: Pneumonia is considered a focus of infection in patients presenting with community-acquired bacterial meningitis but the impact on disease course is unclear. The aim was to study presenting characteristics, clinical course and outcome of meningitis patients with co-existing pneumonia on admission. METHODS: We evaluated adult patients with community-acquired bacterial meningitis with pneumonia on admission in a nationwide, prospective cohort performed from March 2006 to June 2017. We performed logistic regression analysis to identify clinical characteristics predictive of pneumonia on admission, and to quantify the effect of pneumonia on outcome. RESULTS: Pneumonia was diagnosed on admission in 315 of 1852 (17%) bacterial meningitis episodes and confirmed by chest X-ray in 256 of 308 (83%) episodes. Streptococcus pneumoniae was the causative organism in 256 of 315 episodes (81%). Pneumonia on admission was associated with advanced age (OR 1.03 per year increase, 95% CI 1.02-1.04, p < 0.001), alcoholism (OR 1.96, 95% CI 1.23-3.14, p 0.004), cancer (OR 1.54, 95% CI 1.12-2.13, p 0.008), absence of otitis or sinusitis (OR 0.44, 95% CI 0.32-0.59, p < 0.001) and S. pneumoniae (OR 2.14, 95% CI 1.55-2.95, p < 0.001) in the multivariate analysis. An unfavourable outcome defined as a score of 1-4 on the Glasgow Outcome Scale was observed in 172 (55%) episodes and 87 patients (28%) died. Pneumonia on admission was independently associated with unfavourable outcome and mortality in the multivariate analysis (OR 1.48, 95% CI 1.12-1.96; p 0.005). CONCLUSION: Pneumonia on admission in bacterial meningitis is a frequent coexisting infection and is independently associated with unfavourable outcome and mortality.


Assuntos
Infecções Comunitárias Adquiridas/microbiologia , Meningites Bacterianas/complicações , Pneumonia/microbiologia , Idoso , Antibacterianos/uso terapêutico , Feminino , Humanos , Modelos Logísticos , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/tratamento farmacológico , Pessoa de Meia-Idade , Países Baixos , Pneumonia/diagnóstico por imagem , Estudos Prospectivos , Radiografia , Fatores de Risco
5.
J Infect ; 77(1): 54-59, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29746949

RESUMO

OBJECTIVE: To study whether genetic variation in coagulation and fibrinolysis genes contributes to cerebrovascular complications in bacterial meningitis. METHODS: We performed a nationwide prospective genetic association study in adult community-acquired bacterial meningitis patients. The exons and flanking regions of 16 candidate genes involved in coagulation and fibrinolysis pathways were sequenced. We analyzed whether genetic variation in these genes resulted in a higher risk of cerebrovascular complications, unfavorable outcome and differences in thrombocyte count on admission. RESULTS: From 2006 to 2011, a total of 1101 bacterial meningitis patients were identified of whom 622 supplied DNA for genotyping and passed genetic quality control steps. In 139 patients (22%) the episode of bacterial meningitis was complicated by cerebral infarction, and 188 (30%) had an unfavorable outcome. We identified the functional variant rs494860 in the protein Z (PROZ) gene as our strongest association with occurrence of cerebral infarction (odds ratio (OR) 0.49 (95% confidence interval 0.33-0.73), p = 5.2 × 10-4). After Bonferroni correction for multiple testing no genetic variant was significantly associated (p-value threshold 2.7 × 10-4). CONCLUSION: Our study suggests a functional genetic variation in the PROZ gene, rs494860, may be of importance in bacterial meningitis pathogenesis and cerebral infarction risk. Replication of this finding in other cohort studies populations is needed.


Assuntos
Coagulação Sanguínea/genética , Transtornos Cerebrovasculares/etiologia , Fibrinólise/genética , Estudos de Associação Genética , Meningites Bacterianas/complicações , Meningite Pneumocócica/complicações , Adulto , Idoso , Infarto Cerebral/epidemiologia , Infarto Cerebral/etiologia , Transtornos Cerebrovasculares/microbiologia , Estudos de Coortes , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Variação Genética , Humanos , Masculino , Meningites Bacterianas/epidemiologia , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Razão de Chances , Estudos Prospectivos , Análise de Sequência de DNA
6.
Ned Tijdschr Geneeskd ; 161: D1456, 2017.
Artigo em Holandês | MEDLINE | ID: mdl-28745253

RESUMO

BACKGROUND: Meningococcal disease usually presents as meningitis and/or septicaemia, but can also present as pneumonia or arthritis. Since 2000, a worldwide increase in meningococcal disease is reported which is caused by a new virulent clone of serogroup W (MenW:cc11). This subtype is more likely to give an atypical clinical presentation and results in high mortality rates. CASE DESCRIPTION: A 68-year-old woman with polymyalgia rheumatica, managed with prednisone, developed an acute gastrointestinal syndrome of nausea, diarrhoea, vomiting, fever and chills. She presented at the Emergency Department and was admitted to intensive care for septic shock. Blood cultures revealed MenW:cc11 infection. She received antibiotic treatment and left the hospital in good condition 8 days after admission. CONCLUSION: MenW:cc11 is associated with gastrointestinal symptoms and sepsis. Recognition of this atypical clinical presentation is important for a timely and adequate treatment and for antibiotic prophylaxis of family members and close contacts.


Assuntos
Gastroenteropatias/diagnóstico , Infecções Meningocócicas/diagnóstico , Neisseria meningitidis , Idoso , Feminino , Febre , Gastroenteropatias/microbiologia , Humanos , Sepse , Sorogrupo
7.
Clin Microbiol Infect ; 23(8): 573.e1-573.e7, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28192234

RESUMO

OBJECTIVES: Current information on rates and dynamics of meningococcal carriage is essential for public health policy. This study aimed to determine meningococcal carriage prevalence, its risk factors and duration in the Netherlands, where meningococcal C vaccine coverage is >90%. Several methods to identify serogroups of meningococcal carriage isolates among adolescent and young adults were compared. METHODS: Oropharyngeal swabs were collected from 1715 participants 13-23 years of age in 2013-2014; 300 were prospectively followed over 8 months. Cultured isolates were characterized by Ouchterlony, real-time (rt-) PCR or whole-genome sequencing (WGS). Direct swabs were assessed by rt-PCR. Questionnaires on environmental factors and behaviour were also obtained. RESULTS: A meningococcal isolate was identified in 270/1715 (16%) participants by culture. Of MenB isolates identified by whole genome sequencing, 37/72 (51%) were correctly serogrouped by Ouchterlony, 46/51 (90%) by rt-PCR of cultured isolates, and 39/51 (76%) by rt-PCR directly on swabs. A sharp increase in carriage was observed before the age of 15 years. The age-related association disappeared after correction for smoking, level of education, frequent attendance to crowded social venues, kissing in the previous week and alcohol consumption. Three participants carried the same strain identified at three consecutive visits in an 8-month period. In these isolates, progressively acquired mutations were observed. CONCLUSIONS: Whole genome sequencing of culture isolates was the most sensitive method for serogroup identification. Based upon results of this study and risk of meningococcal disease, an adolescent meningococcal vaccination might include children before the age of 15 years to confer individual protection and potentially to establish herd protection.


Assuntos
Portador Sadio/epidemiologia , Infecções Meningocócicas/epidemiologia , Neisseria meningitidis/isolamento & purificação , Orofaringe/microbiologia , Adolescente , Portador Sadio/microbiologia , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Infecções Meningocócicas/microbiologia , Neisseria meningitidis/classificação , Países Baixos/epidemiologia , Prevalência , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Sorogrupo , Sorotipagem , Inquéritos e Questionários , Fatores de Tempo , Sequenciamento Completo do Genoma , Adulto Jovem
8.
Clin Microbiol Infect ; 23(4): 265.e1-265.e7, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27998823

RESUMO

OBJECTIVES: Listeria monocytogenes is a food-borne pathogen that can cause meningitis. The listerial genotype ST6 has been linked to increasing rates of unfavourable outcome over time. We investigated listerial genetic variation and the relation with clinical outcome in meningitis. METHODS: We sequenced 96 isolates from adults with listerial meningitis included in two prospective nationwide cohort studies by whole genome sequencing, and evaluated associations between bacterial genetic variation and clinical outcome. We validated these results by screening listerial genotypes of 445 cerebrospinal fluid and blood isolates from patients over a 30-year period from the Dutch national surveillance cohort. RESULTS: We identified a bacteriophage, phiLMST6 co-occurring with a novel plasmid, pLMST6, in ST6 isolates to be associated with unfavourable outcome in patients (p 2.83e-05). The plasmid carries a benzalkonium chloride tolerance gene, emrC, conferring decreased susceptibility to disinfectants used in the food-processing industry. Isolates harbouring emrC were growth inhibited at higher levels of benzalkonium chloride (median 60 mg/L versus 15 mg/L; p <0.001), and had higher MICs for amoxicillin and gentamicin compared with isolates without emrC (both p <0.001). Transformation of pLMST6 into naive strains led to benzalkonium chloride tolerance and higher MICs for gentamicin. CONCLUSIONS: These results show that a novel plasmid, carrying the efflux transporter emrC, is associated with increased incidence of ST6 listerial meningitis in the Netherlands. Suggesting increased disease severity, our findings warrant consideration of disinfectants used in the food-processing industry that select for resistance mechanisms and may, inadvertently, lead to increased risk of poor disease outcome.


Assuntos
Anti-Infecciosos Locais/farmacologia , Compostos de Benzalcônio/farmacologia , Farmacorresistência Bacteriana , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/genética , Meningite por Listeria/microbiologia , Meningite por Listeria/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Estudos de Coortes , Feminino , Variação Genética , Genoma Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Listeria monocytogenes/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Países Baixos , Avaliação de Resultados da Assistência ao Paciente , Filogenia , Plasmídeos/genética , Polimorfismo de Nucleotídeo Único , Vigilância da População , Adulto Jovem
9.
Clin Microbiol Infect ; 23(2): 121.e9-121.e15, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27816734

RESUMO

OBJECTIVES: To investigate sex-based differences in clinical features, causative pathogens, outcome and treatment of adult community-acquired meningitis. METHODS: From January 2006 to July 2014, we prospectively investigated sex-based differences in clinical features, causative pathogens, outcome and treatment of adult community-acquired meningitis in a nationwide cohort study in the Netherlands. Sex was analysed along with known predictors of unfavourable outcome using logistic regression. RESULTS: We evaluated 1412 episodes of meningitis, 707 (50%) in men. Men more often presented with a history of remote head injury (41/667 (6%) versus 14/658 (2%) women, p 0.0002) or alcoholism (61/652 (9%) versus 21/660 (3%) women, p <0.0001). Neck stiffness was less common in men (453/651 (70%) versus 524/671 (78%) women, p 0.0004). Despite greater illness severity, women were less likely to receive treatment in an intensive care unit (odds ratio (OR) 0.72, 95% CI 0.58-0.89, p 0.003) or mechanical ventilation (OR 0.67, 95% CI 0.54-0.85, p 0.001). Women exhibited higher serum inflammatory parameters than men (median C-reactive protein 211 versus 171, p 0.0001; median erythrocyte sedimentation rate 48 versus 33, p <0.0001). Corticosteroids improved prognosis in both sexes, but absolute risk reduction was higher in women (20% versus 15%, p 0.001), although we found no significant interaction between sex and dexamethasone (p 0.38). In the multivariable analysis, male sex was an independent predictor of unfavourable outcome (OR 1.34, 95% CI 1.03-1.75, p 0.03) and death (OR 1.47, 95% CI 1.04-2.07, p 0.03). CONCLUSIONS: Our findings show sex-based differences in adults with community-acquired bacterial meningitis. Male sex is an independent risk factor for adverse outcome. It is possible that sex-based differences in immune reaction could determine a distinct response to corticosteroids.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Meningites Bacterianas/epidemiologia , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Biomarcadores , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Comorbidade , Feminino , Humanos , Masculino , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/microbiologia , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Razão de Chances , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do Tratamento , Adulto Jovem
10.
Expert Opin Investig Drugs ; 25(11): 1325-1335, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27676206

RESUMO

INTRODUCTION: To date, the management of patients with suspected or confirmed Ebolavirus disease (EVD) depends on quarantine, symptomatic management and supportive care, as there are no approved vaccines or treatments available for human use. However, accelerated by the recent large outbreak in West Africa, significant progress has been made towards vaccine development but also towards specific treatment with convalescent plasma and monoclonal antibodies. Areas covered: We describe recent developments in monoclonal antibody treatment for EVD, encompassing mAb114 and the MB-003, ZMAb, ZMapp™ and MIL-77E cocktails. Expert opinion: Preventive measures, are, and will remain essential to curb EVD outbreaks; even more so with vaccine development progressing. However, research for treatment options must not be neglected. Small-scale animal and individual human case studies show that monoclonal antibodies (mAbs) can be effective for EVD treatment; thus justifying exploration in clinical trials. Potential limitations are that high doses may be needed to yield clinical efficacy; epitope mutations might reduce efficacy; and constant evolution of (outbreak-specific) mAb mixtures might be required. Interim advice based on the clinical experience to date is that treatment of patients with mAbs is sensible, provided those could be made available in the necessary amounts in time.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Desenho de Fármacos , Doença pelo Vírus Ebola/tratamento farmacológico , Animais , Anticorpos Monoclonais/farmacologia , Surtos de Doenças , Vacinas contra Ebola/imunologia , Epitopos/genética , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/imunologia , Humanos , Mutação
11.
Clin Microbiol Infect ; 22(11): 928-933, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27484018

RESUMO

OBJECTIVES: To study the impact of an evidence-based guideline on the management of community-acquired bacterial meningitis. METHODS: We performed an interrupted time series analysis in a prospective nationwide cohort study from 2006 to 2015. The guideline stresses the importance of cranial imaging before lumbar puncture (LP) in selected patients based on clinical criteria, and early treatment with amoxicillin and a third-generation cephalosporin for adults with suspected community-acquired bacterial meningitis. The guideline was published in April 2013. RESULTS: We included 1326 episodes before and 210 episodes after guideline introduction. Cranial imaging was performed before LP in 497 (84%) of 591 episodes with clinical criteria warranting computed tomography (CT). The guideline did not improve this (increase of 2%; 95% confidence interval (CI), -15 to 19). Without these criteria, imaging before LP occurred in 606 (67%) of 900 episodes, also without effect of the guideline (increase of 1%; 95% CI, -25 to 28). The estimate of effect of the guideline for treatment with the recommended antibiotic regimen was an increase of 19.5% (95% CI, 13.5 to 25.5), and there was a trend towards more frequent initiation of treatment before CT. There was no association between delay in antibiotic treatment due to imaging before LP and unfavourable outcome (odds ratio, 1.14; 95% CI 0.86 to 1.52). CONCLUSIONS: Cranial imaging is performed before LP in the majority of patients with bacterial meningitis, irrespective of guideline indications. The guideline introduction was associated with a trend towards early initiation of treatment before imaging and with increased adherence to antibiotic policy.


Assuntos
Amoxicilina/administração & dosagem , Encéfalo/diagnóstico por imagem , Cefalosporinas/administração & dosagem , Meningites Bacterianas/tratamento farmacológico , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Adolescente , Adulto , Idoso , Amoxicilina/uso terapêutico , Infecções Comunitárias Adquiridas/diagnóstico por imagem , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/patologia , Gerenciamento Clínico , Medicina Baseada em Evidências , Humanos , Análise de Séries Temporais Interrompida , Meningites Bacterianas/diagnóstico por imagem , Meningites Bacterianas/patologia , Pessoa de Meia-Idade , Países Baixos , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Punção Espinal/estatística & dados numéricos , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
12.
Bone Marrow Transplant ; 51(11): 1490-1495, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27376451

RESUMO

We performed a nationwide prospective cohort study on the epidemiology and clinical features of community-acquired bacterial meningitis. Patients with a medical history of autologous or allogeneic hematopoietic stem cell transplantation (HSCT) were identified from the cohort performed from March 2006 to October 2014. Fourteen of 1449 episodes (1.0%) of bacterial meningitis occurred in patients with a history of HSCT. The incidence of bacterial meningitis in HSCT recipients was 40.4 per 100 000 patients per year (95% confidence interval (CI) 23.9-62.2), which is 30-fold (95% CI 18-51; P<0.001) higher compared with persons without HSCT. Incidence was higher in allogeneic HSCT compared with autologous HSCT (70.0 vs 15.8 per 100 000 patients per year). Causative organisms were Streptococcus pneumoniae in 11 patients, Neisseria meningitidis in two and Streptococcus mitis in one patient. Mortality was 3 of 14 (21%) and 6 of 11 (55%) survivors had sequelae. Nine of 11 patients (82%) with pneumococcal meningitis were infected with a serotype included in the 23-valent pneumococcal polysaccharide vaccine, of whom four developed meningitis despite vaccination. In conclusion, HSCT recipients have a substantially increased risk compared with the general population of acquiring bacterial meningitis, which is mostly due to S. pneumoniae, and disease is associated with high mortality and morbidity. Vaccination is important to prevent disease although vaccine failures did occur.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Meningites Bacterianas/epidemiologia , Infecções Comunitárias Adquiridas , Humanos , Meningites Bacterianas/microbiologia , Meningites Bacterianas/prevenção & controle , Medição de Risco , Streptococcus pneumoniae , Vacinação
13.
Transpl Infect Dis ; 18(5): 674-680, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27385317

RESUMO

BACKGROUND: Solid organ transplant (SOT) recipients are at risk of infections of the central nervous system. However, the incidence and clinical course of bacterial meningitis in SOT recipients are unclear. We studied occurrence, disease course, and prognosis of bacterial meningitis in SOT recipients in the Netherlands. METHODS: All patients with a medical history of solid organ transplantation were selected from our nationwide prospective cohort study on community-acquired bacterial meningitis in patients >16 years old, performed from March 1, 2006 to October 31, 2014. Data on patient history, symptoms and signs on admission, treatment, and outcome were collected prospectively. For transplant recipients, additional information was collected retrospectively. RESULTS: We identified 6 SOT recipients, all receiving renal transplants. The annual incidence of bacterial meningitis was 7-fold higher (95% confidence interval [CI] 2.94-17.02, P < 0.001) for renal transplant recipients as compared with the general population (9.56 [95% CI 3.98-22.96] vs. 1.35 [95% CI 1.28-1.43] per 100,000 patients per year). One of the 6 patients (17%) presented with the classic presentation of bacterial meningitis (fever, neck stiffness, and change in mental status). Seizures were common, occurring in 33% of patients. Streptococcus pneumoniae and Listeria monocytogenes were identified in 2 patients each, and Escherichia coli and Pseudomonas aeruginosa were both identified once. Four of 6 patients (67%) had an unfavorable functional outcome. CONCLUSION: Bacterial meningitis is a rare but devastating complication of solid organ transplantation. SOT recipients are at high risk for developing meningitis, and recognition of this condition may be difficult, owing to atypical clinical manifestation.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Transplante de Rim/efeitos adversos , Meningites Bacterianas/epidemiologia , Transplantados/estatística & dados numéricos , Adulto , Idoso , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/etiologia , Infecções Comunitárias Adquiridas/microbiologia , Escherichia coli/isolamento & purificação , Feminino , Humanos , Incidência , Listeria monocytogenes/isolamento & purificação , Masculino , Meningites Bacterianas/complicações , Meningites Bacterianas/etiologia , Meningites Bacterianas/microbiologia , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prognóstico , Estudos Prospectivos , Pseudomonas aeruginosa/isolamento & purificação , Estudos Retrospectivos , Fatores de Risco , Streptococcus pneumoniae/isolamento & purificação
14.
Sci Rep ; 6: 28984, 2016 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-27381348

RESUMO

Streptococcus suis is a zoonotic swine pathogen and a major public health concern in Asia, where it emerged as an important cause of bacterial meningitis in adults. While associated with food-borne transmission in Asia, zoonotic S. suis infections are mainly occupational hazards elsewhere. To identify genomic differences that can explain zoonotic potential, we compared whole genomes of 98 S. suis isolates from human patients and pigs with invasive disease in the Netherlands, and validated our observations with 18 complete and publicly available sequences. Zoonotic isolates have smaller genomes than non-zoonotic isolates, but contain more virulence factors. We identified a zoonotic S. suis clone that diverged from a non-zoonotic clone by means of gene loss, a capsule switch, and acquisition of a two-component signalling system in the late 19th century, when foreign pig breeds were introduced. Our results indicate that zoonotic potential of S. suis results from gene loss, recombination and horizontal gene transfer events.


Assuntos
Infecções Estreptocócicas/microbiologia , Streptococcus suis/genética , Fatores de Virulência/genética , Virulência/genética , Zoonoses/microbiologia , Animais , Genômica/métodos , Interações Hospedeiro-Patógeno/genética , Humanos , Meningites Bacterianas/microbiologia , Países Baixos , Suínos/microbiologia , Doenças dos Suínos/microbiologia
15.
Clin Microbiol Infect ; 22(5): 428-33, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26802211

RESUMO

In a prospective nationwide cohort study performed in the Netherlands from 2006 to 2014 we analysed clinical and laboratory characteristics of adults with community-acquired bacterial meningitis who underwent repeat lumbar puncture. Repeat lumbar puncture was performed in 124 of 1490 included episodes (8%), most commonly because of clinical deterioration (42%). Median cerebrospinal fluid (CSF) leucocyte count on admission was 1473 cells/mm(3). Median CSF cell count showed a decrease of 19% when repeated within 2 days; of 84% within 3-7 days, of 93% within 8-14 days and of 98% within 15-21 days. Repeat lumbar puncture confirmed the diagnosis of meningitis in eight patients with normal initial CSF examination. Repeat CSF cultures yielded bacteria in nine patients, which led to identification of an underlying source of infection in two. We conclude that repeat lumbar puncture is performed in a small proportion of adults. Although it should not be seen as routine it can be useful in selected cases to confirm diagnosis, to exclude relapsing or persistent infection, or for therapeutic purpose in communicating hydrocephalus.


Assuntos
Testes Diagnósticos de Rotina/métodos , Meningites Bacterianas/diagnóstico , Punção Espinal/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bactérias/classificação , Bactérias/isolamento & purificação , Líquido Cefalorraquidiano/citologia , Líquido Cefalorraquidiano/microbiologia , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Países Baixos , Estudos Prospectivos , Adulto Jovem
17.
Zoonoses Public Health ; 63(6): 442-8, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26693951

RESUMO

Bacterial meningitis is a disease with a high morbidity and mortality. It may be caused by the zoonotic pathogen Capnocytophaga canimorsus, which is part of the commensal oral flora in dogs and cats. We report three cases of C. canimorsus meningitis in a nationwide cohort study of bacterial meningitis patients and performed a review of the literature. Three episodes of C. canimorsus meningitis were identified in three patients included in a nationwide cohort study from 2006 through 2014. The calculated annual incidence was 0.03 per million adults. When combined with the literature, 33 patients were identified of which 28 were male (85%). The median age was 63 years, and 13 (42%) were immunocompromised, which consisted of alcoholism in 7 (21%). Animal contact could be established in 29 of 30 patients (93%) and consisted of dog bites in 22 of 29 (76%). One patient died (3%) and 8 had neurological sequelae upon discharge (25%), most often hearing loss (n = 6, 19%). Capnocytophaga canimorsus meningitis is associated with dog bites. Although mortality is relatively low, survivors often have neurological sequelae.


Assuntos
Infecções por Flavobacteriaceae/microbiologia , Meningites Bacterianas/microbiologia , Adulto , Idoso , Animais , Cães , Flavobacteriaceae , Infecções por Flavobacteriaceae/patologia , Humanos , Masculino , Meningites Bacterianas/etiologia , Pessoa de Meia-Idade , Zoonoses
18.
J Thromb Haemost ; 13(11): 2076-86, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26340319

RESUMO

BACKGROUND: Mortality and morbidity in patients with bacterial meningitis result from the proinflammatory response and dysregulation of coagulation and fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI) is activated by free thrombin or thrombin in complex with thrombomodulin, and plays an antifibrinolytic role during fibrin clot degradation, but also has an anti-inflammatory role by inactivating proinflammatory mediators, such as complement activation products. OBJECTIVE: To assess the role of TAFI in pneumococcal meningitis. METHODS: We performed a prospective nationwide genetic association study in patients with bacterial meningitis, determined TAFI and complement levels in cerebrospinal fluid (CSF), and assessed the function of TAFI in a pneumococcal meningitis mouse model by using Cpb2 (TAFI) knockout mice. RESULTS: Polymorphisms (reference sequences: rs1926447 and rs3742264) in the CPB2 gene, coding for TAFI, were related to the development of systemic complications in patients with pneumococcal meningitis. Higher protein levels of TAFI in CSF were significantly associated with CSF complement levels (C3a, iC3b, and C5b-9) and with more systemic complications in patients with bacterial meningitis. The risk allele of rs1926447 (TT) was associated with higher levels of TAFI in CSF. In the murine model, consistent with the human data, Cpb2-deficient mice had decreased disease severity, as reflected by lower mortality, and attenuated cytokine levels and bacterial outgrowth in the systemic compartment during disease, without differences in the brain compartment, as compared with wild-type mice. CONCLUSIONS: These findings suggest that TAFI plays an important role during pneumococcal meningitis, which is likely to be mediated through inhibition of the complement system, and influences the occurrence of systemic complications and inflammation.


Assuntos
Carboxipeptidase B2/fisiologia , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Pneumocócica/líquido cefalorraquidiano , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Animais , Dano Encefálico Crônico/etiologia , Carboxipeptidase B2/líquido cefalorraquidiano , Carboxipeptidase B2/deficiência , Carboxipeptidase B2/genética , Hemorragia Cerebral/etiologia , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/líquido cefalorraquidiano , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/genética , Complemento C3a/líquido cefalorraquidiano , Complemento C3b/líquido cefalorraquidiano , Complexo de Ataque à Membrana do Sistema Complemento/líquido cefalorraquidiano , Citocinas/sangue , Feminino , Fibrinólise , Humanos , Masculino , Meningite Meningocócica/sangue , Meningite Meningocócica/complicações , Meningite Meningocócica/genética , Meningite Pneumocócica/sangue , Meningite Pneumocócica/complicações , Meningite Pneumocócica/genética , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Insuficiência Respiratória/etiologia , Choque Séptico/etiologia , Resultado do Tratamento
19.
Clin Microbiol Infect ; 21(12): 1077-83, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26314916

RESUMO

We describe the incidence and patient characteristics of Streptococcus gallolyticus meningitis. We identified S. gallolyticus meningitis in a nationwide cohort of patients with community-acquired bacterial meningitis, and performed a systematic review and meta-analysis of all reported adult cases in the literature. Five cases were identified (0.3%) in a cohort of 1561 episodes of bacterial meningitis. In one patient, bowel disease (colon polyps) was identified as a predisposing condition for S. gallolyticus infection, whereas no patients were diagnosed with endocarditis. In a combined analysis of our patients and 37 reported in the literature, we found that the median age was 59 years. Predisposing factors were present in 21 of 42 patients (50%), and mainly consisted of immunosuppressive therapy (seven patients), cancer (four patients), and alcoholism (four patients). Colon disease was identified in 15 of 24 patients (63%) and endocarditis in five of 27 patients (18%). Co-infection with Strongyloides stercoralis was identified in 14 of 34 patients (41%), ten of whom were infected with human immunodeficiency virus or human T-lymphotropic virus. Outcomes were described for 37 patients; eight died (22%) and one (3%) had neurological sequelae. S. gallolyticus is an uncommon cause of bacterial meningitis, with specific predisposing conditions. When it is identified, consultation with a cardiologist and gastroenterologist is warranted to rule out underlying endocarditis or colon disease. Stool examinations for Strongyloides stercoralis should be performed in patients who have travelled to or originate from endemic areas.


Assuntos
Meningites Bacterianas/epidemiologia , Infecções Estreptocócicas/epidemiologia , Streptococcus/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/epidemiologia , Fezes/microbiologia , Feminino , Humanos , Incidência , Masculino , Meningites Bacterianas/microbiologia , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Estudos Prospectivos , Fatores de Risco , Infecções Estreptocócicas/microbiologia , Streptococcus/classificação
20.
Euro Surveill ; 20(31)2015 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-26290429

RESUMO

Although the disease burden of listeriosis on population level is low, on individual level the impact is high, largely due to severe illness and a high case fatality. Identification of risk factors supports and specifies public health actions needed for prevention. We performed a case­control study to determine host- and food-related risk factors for non-perinatal listeriosis in the Netherlands. Patients with non-perinatal listeriosis reported between July 2008 and December 2013 were compared with controls from a periodic control survey who completed a questionnaire in the same period. Higher age, male sex, underlying disease, especially cancer and kidney disease, and use of immunosuppressive medicine were strong risk factors for acquiring non-perinatal listeriosis. Analysis of the food consumption in the group of cases and controls with underlying diseases did not reveal any high-risk food products. Information and advice should continue to be given to persons at risk of severe listeriosis. Univariate analyses indicate that patients using gastric acid inhibitors are at risk. It is worth adding these patients to the group of susceptible persons.


Assuntos
Contaminação de Alimentos , Microbiologia de Alimentos , Listeria monocytogenes/isolamento & purificação , Listeriose/diagnóstico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Comportamento Alimentar , Feminino , Humanos , Listeriose/epidemiologia , Listeriose/microbiologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Fatores de Risco , Distribuição por Sexo , Inquéritos e Questionários , Adulto Jovem
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