RESUMO
Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for N. meningitidis, S. pneumoniae, and H. influenzae used in routine meningitis surveillance. A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and Plasmodium. Overall, Escherichia coli was the most prevalent (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and Plasmodium detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.
Assuntos
Infecções por Escherichia coli/epidemiologia , Malária Cerebral/epidemiologia , Meningite Pneumocócica/epidemiologia , Meningite/epidemiologia , Meningite/microbiologia , África Ocidental/epidemiologia , Pré-Escolar , Técnicas de Cultura , Infecções por Citomegalovirus/líquido cefalorraquidiano , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Infecções por Escherichia coli/líquido cefalorraquidiano , Infecções por Escherichia coli/diagnóstico , Feminino , Gana/epidemiologia , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Vacinas Anti-Haemophilus/uso terapêutico , Humanos , Lactente , Recém-Nascido , Infecções por Klebsiella/líquido cefalorraquidiano , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/epidemiologia , Malária Cerebral/líquido cefalorraquidiano , Malária Cerebral/diagnóstico , Masculino , Meningite/líquido cefalorraquidiano , Meningite/diagnóstico , Meningite por Haemophilus/líquido cefalorraquidiano , Meningite por Haemophilus/epidemiologia , Meningite por Haemophilus/prevenção & controle , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/epidemiologia , Meningite Meningocócica/prevenção & controle , Meningite Pneumocócica/líquido cefalorraquidiano , Meningite Pneumocócica/prevenção & controle , Vacinas Meningocócicas/uso terapêutico , Técnicas de Diagnóstico Molecular , Mortalidade , Reação em Cadeia da Polimerase Multiplex , Níger/epidemiologia , Nigéria/epidemiologia , Vacinas Pneumocócicas/uso terapêutico , Reação em Cadeia da Polimerase em Tempo Real , Infecções por Roseolovirus/líquido cefalorraquidiano , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/epidemiologia , Senegal/epidemiologia , Infecções Estafilocócicas/líquido cefalorraquidiano , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/epidemiologia , Togo/epidemiologiaRESUMO
Bacterial meningitis is a public health crisis in the northern part of Ghana, where it contributes to very high mortality and morbidity rates. Early detection of the causative organism will lead to better management and effective treatment. Our aim was to evaluate the diagnostic accuracy of Pastorex and Wellcogen latex agglutination tests for the detection of bacterial meningitis in a resource-limited setting. CSF samples from 330 suspected meningitis patients within the northern zone of Ghana were analysed for bacterial agents at the zonal Public Health Reference Laboratory in Tamale using polymerase chain reaction (PCR) and two latex agglutination test kits; Pastorex and Wellcogen. The overall positivity rate of samples tested for bacterial meningitis was 46.4%. Streptococcus pneumoniae was the most common cause of bacterial meningitis within the sub-region, with positivity rate of 25.2%, 28.2% and 28.8% when diagnosed using Wellcogen, Pastorex and PCR respectively. The Pastorex method was 97.4% sensitive while the Wellcogen technique was 87.6% sensitive. Both techniques however produced the same specificity of 99.4%. Our study revealed that the Pastorex method has a better diagnostic value for bacterial meningitis than the Wellcogen method and should be the method of choice in the absence of PCR.
Assuntos
Testes de Fixação do Látex/métodos , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/microbiologia , Reação em Cadeia da Polimerase em Tempo Real , Adolescente , Adulto , Técnicas de Tipagem Bacteriana , Criança , Pré-Escolar , Feminino , Gana , Humanos , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Meningite por Haemophilus/líquido cefalorraquidiano , Meningite por Haemophilus/diagnóstico , Meningite por Haemophilus/microbiologia , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/diagnóstico , Meningite Meningocócica/microbiologia , Meningite Pneumocócica/líquido cefalorraquidiano , Meningite Pneumocócica/diagnóstico , Meningite Pneumocócica/microbiologia , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Sorotipagem , Infecções Estreptocócicas/líquido cefalorraquidiano , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/genética , Streptococcus agalactiae/isolamento & purificação , Adulto JovemRESUMO
INTRODUCTION: In sub Saharan Africa, the epidemiology, including the distribution of serogroups of strains of N. meningitidis is poorly investigated in countries outside "the meningitis belt". This study was conducted with the aim to determine the distribution of serogroups of strains of N. meningitidis causing meningococcal meningitis in children and adults in Mozambique. METHODS: A total of 106 PCR confirmed Neisseria meningitidis Cerebrospinal Fluid (CSF) samples or isolates were obtained from the biobank of acute bacterial meningitis (ABM) surveillance being implemented by the National Institute of Health, at three central hospitals in Mozambique, from January to December 2014. Serogroups of N. meningitidis were determined using conventional PCR, targeting siaD gene for Neisseria meningitidis. Outer Membrane Proteins (OMP) Genotyping was performed by amplifying porA gene in nine samples. RESULTS: Of the 106 PCR confirmed Neisseria meningitidis samples, the most frequent serotype was A (50.0%, 53/106), followed by W/Y (18.9%, 20/106), C (8.5%, 9/106), X (7.5%, 8/106) and B (0.9%, 1/106). We found non-groupable strains in a total of 15 (14.2%) samples. PorA genotypes from nine strains showed expected patterns with the exception of two serogroup C strains with P1.19,15,36 and P1.19-36,15 and one serogroup X with P1.19,15,36, variants frequently associated to serogroup B. CONCLUSION: Our data shows that the number of cases of meningococcal meningitis routinely reported in central hospitals in Mozambique is significant and the most dominant serogroup is A. In conclusion, although serogroup A has almost been eliminated from the "meningitis belt", this serogroup remains a major concern in countries outside the belt such as Mozambique.
Assuntos
Meningite Meningocócica/microbiologia , Neisseria meningitidis/genética , Neisseria meningitidis/imunologia , Adolescente , Adulto , Técnicas de Tipagem Bacteriana/métodos , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/epidemiologia , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas/uso terapêutico , Moçambique/epidemiologia , Neisseria meningitidis/classificação , Neisseria meningitidis/isolamento & purificação , Neisseria meningitidis Sorogrupo W-135/genética , Neisseria meningitidis Sorogrupo W-135/imunologia , Reação em Cadeia da Polimerase , Vacinação/métodos , Adulto JovemRESUMO
BACKGROUND: Meningococcal disease (MD) is notoriously difficult to diagnose in the early stages of the illness and presents similarly to many self-limiting viral infections. This mandates a cautious approach to diagnosis and initial management of suspected MD with many children receiving precautionary broad-spectrum intravenous antibiotics. Despite this approach, some children are still diagnosed late. In the last 10 years, there have been advances in nucleic acid amplification techniques, and there is now a rapid test that can detect meningococcal DNA in under 30 min. This Loop-mediated-isothermal AMPlification (LAMP) technology may make it possible to diagnose MD at initial presentation thereby greatly improving outcomes and minimising harms through unnecessary treatment. The aim of this systematic review is to determine the diagnostic accuracy of LAMP technology in cases of suspected MD. The review has been registered with PROSPERO [CRD42017078026]. METHODS: To identify relevant studies, we will search MEDLINE, Embase, Web of Science, Scopus and The Cochrane Library. In additional, we will hand-search reference lists and grey literature including contacting the manufacturers of commercially available LAMP tests for MD for any unpublished data. Two reviewers will independently screen study eligibility and extract data. Methodological quality will be assessed, by two authors, according to the revised tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2); any discrepancies will be resolved by a third author. The following test characteristics will be extracted into 2 × 2 tables for all included studies: true positives, false positives, true negatives, and false negatives. Study-specific estimates of sensitivity and specificity with 95% confidence intervals will be displayed in forest plots. To investigate heterogeneity, we will include covariates such as age, sample type, and study type into a bivariate random-effects model. DISCUSSION: This review will help determine the diagnostic accuracy of LAMP technology in diagnosing MD from blood, CSF and throat swabs in children. The data will help to define where in the diagnostic pathway LAMP could be useful including potential as a point-of-care test for children at first presentation.
Assuntos
Testes Diagnósticos de Rotina/normas , Meningite Meningocócica/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/métodos , Valor Preditivo dos Testes , Criança , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Humanos , Meningite Meningocócica/sangue , Meningite Meningocócica/líquido cefalorraquidiano , Neisseria meningitidis/genética , Neisseria meningitidis/isolamento & purificação , Sensibilidade e EspecificidadeRESUMO
Surface-enhanced Raman spectroscopy (SERS) has been widely used in a variety of biomedical, analytical, forensic and environmental investigations due to its chemical specificity, label-free nature combined with high sensitivity. Here, we report a simple method for the fabrication of reproducible and reliable, well-defined, stable SERS substrates with uniform and giant Raman enhancement suitable for routine trace chemical analysis and detection of biological compounds in complex biological fluids. We prepared porous silicone (PS) surface by a galvanostatic anodic etch of crystalline silicon wafers. The electrochemical process generates a specific layer of PS: the thickness and porosity of a given layer is controlled by the current density, the duration of the etch cycle, and the composition of the etchant solution. These substrates presented high sensitivity to p-mercaptobenzoic acid (p-MBA) at a low concentration of 10-6M and the enhancement factor of over 108 was achieved. Such high enhancement is attributed to semiconducting silicon-induced and stabilized hot spots. The uniform distribution of SERS-active 'hot-spots' on the Au/Si surface results in high reproducibility towards detecting p-MBA at 40 different, randomly selected positions on a single substrate (RSD=6.7%) and on twenty different SERS substrates prepared under identical conditions (RSD=8%). Designed substrates allow the ultrahigh sensitive and specific detection of human such biofluids as blood, urine and cerebrospinal fluid (CSF) in a reliable, label-free, and reproducible manner. The SERS spectra of these fluids are rich in patient-specific information and can be useful in many analytical and biomedical applications. We have shown that our developed SERS substrates allow the nanomolar detection of neopterin (bacterial infections' marker) in cerebrospinal fluid samples. In order to test the performance of our SERS method in term of low detection limit (LOD), the calibration curve i.e. plot of SERS intensity of the marker band at 695cm-1 versus the concentration of neopterin in CSF was constructed and used to calculate the neopterin concentration in clinical samples. The level of neopterin was significantly higher in CSF samples infected by Neisseria meningitidis, (54nmol/L), compared to normal (control) group, (4.3nmol/L). The high sensitivity, selectivity and stability of obtained SERS-active substrates combined with simple, low-cost, and easy method of producing offer a promising tool for SERS-based analysis in clinical trials.
Assuntos
Benzoatos/análise , Técnicas Biossensoriais/métodos , Líquidos Corporais/química , Ouro/química , Silício/química , Análise Espectral Raman , Compostos de Sulfidrila/análise , Líquidos Corporais/metabolismo , Humanos , Limite de Detecção , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/diagnóstico , Meningite Meningocócica/microbiologia , Nanopartículas Metálicas/química , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Neopterina/sangue , Neopterina/líquido cefalorraquidiano , Neopterina/urina , Reprodutibilidade dos Testes , Propriedades de SuperfícieRESUMO
Invasive meningococcal disease (IMD) is a major public health problem worldwide. An epidemic of serogroup C (NmC) IMD occurred in 2010 in the city of Salvador. In this study, we describe the antigenic and genetic characterization of meningococcal isolates collected from meningitis cases in Salvador from 2001 to 2012. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were performed for the analysis of IMD isolates. A total of 733 cases were identified, and the serogroup was determined for 391 (53.0%) of these. Most cases were caused by NmC (53%) or B (47%). The most prevalent strains were B:4,7:P1.19,15 (32.9%; 129/391) and C:23:P1.14-6 (28.6%; 112/391). Based on PFGE/MLST analysis, 71.3% (77/108 PFGE-tested isolates) clustered as two clones of sequence type ST-3779 and ST-3780, both belonging to the ST-103 clonal complex. ST-3779 has been detected in Salvador since 1996 and together with ST-3780 became predominant after 2005. There was a predominance of C:23:P1.14-6, ST-3779/3780 in Salvador during the period of 2007-2012, establishing a major clonal lineage, which remained in the community for a long time; this has serious implications for public health, particularly in terms of prevention and control strategies of IMD.
Assuntos
Meningite Meningocócica/epidemiologia , Neisseria meningitidis Sorogrupo C/genética , Adolescente , Adulto , Fatores Etários , Brasil/epidemiologia , Criança , Pré-Escolar , Eletroforese em Gel de Campo Pulsado , Feminino , Humanos , Masculino , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/mortalidade , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Neisseria meningitidis/classificação , Neisseria meningitidis/genética , Neisseria meningitidis Sorogrupo C/classificação , Sorogrupo , Sorotipagem , Adulto JovemRESUMO
BACKGROUND: Historically, Neisseria meningitidis serogroup A (NmA) caused large meningitis epidemics in sub-Saharan Africa. In 2010, Burkina Faso became the first country to implement a national meningococcal serogroup A conjugate vaccine (MACV) campaign. We analyzed nationwide meningitis surveillance data from Burkina Faso for the 5 years following MACV introduction. METHODS: We examined Burkina Faso's aggregate reporting and national laboratory-confirmed case-based meningitis surveillance data from 2011-2015. We calculated incidence (cases per 100,000 persons), and described reported NmA cases. RESULTS: In 2011-2015, Burkina Faso reported 20,389 cases of suspected meningitis. A quarter (4,503) of suspected meningitis cases with cerebrospinal fluid specimens were laboratory-confirmed as either S. pneumoniae (57%), N. meningitidis (40%), or H. influenzae (2%). Average adjusted annual national incidence of meningococcal meningitis was 3.8 (range: 2.0-10.2 annually) and was highest among infants aged <1 year (8.4). N. meningitidis serogroup W caused the majority (64%) of meningococcal meningitis among all age groups. Only six confirmed NmA cases were reported in 2011-2015. Five cases were in children who were too young (n = 2) or otherwise not vaccinated (n = 3) during the 2010 MACV mass vaccination campaign; one case had documented MACV receipt, representing the first documented MACV failure. CONCLUSIONS: Meningococcal meningitis incidence in Burkina Faso remains relatively low following MACV introduction. However, a substantial burden remains and NmA transmission has persisted. MACV integration into routine childhood immunization programs is essential to ensure continued protection.
Assuntos
Haemophilus influenzae/isolamento & purificação , Programas de Imunização/métodos , Meningite Meningocócica/prevenção & controle , Neisseria meningitidis Sorogrupo A/isolamento & purificação , Adolescente , Burkina Faso/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/epidemiologia , Meningite Meningocócica/microbiologia , Vacinas MeningocócicasRESUMO
At present, the great attention is given to the neurospecific markers as their elevated level in the cerebrospinal fluid corresponds to the degree of destruction of relevant CNS cells. Therefore, actual direction of the studies of the pathogenesis and diagnosis of CNS diseases is to determine levels of neurospecific markers in the cerebrospinal fluid (CSF). The purpose of the study was to evaluate the diagnostic and prognostic role of NSE, S-100 protein, GFAP and MBP levels in CSF of patients with acute bacterial meningitis. S-100 protein, NSE, GFAP and MBP levels in CSF of patients with acute pneumococcal and meningococcal meningitis were determined during admission and after 10-12 days of treatment. Patients were divided into groups depending on the etiology and severity of the disease. 60 cases of acute bacterial meningitis, as a study group, and 12 cases with acute respiratory infection and meningism, as a control group, were analyzed. It is shown that CSF levels of NSE, S-100 protein, GFAP and MBP on the first day of admission were significantly increased (P<0,05), depending on the severity of the disease. The highest levels of neurospecific markers have been identified in non-survivors (P<0,001). The concentration changes of CSF neurospecific markers are found to be helpful as a diagnostic and prognostic marker in acute bacterial meningitis.
Assuntos
Meningites Bacterianas/líquido cefalorraquidiano , Doença Aguda , Adolescente , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Humanos , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Pneumocócica/líquido cefalorraquidiano , Pessoa de Meia-Idade , Proteína Básica da Mielina/líquido cefalorraquidiano , Fosfopiruvato Hidratase/líquido cefalorraquidiano , Proteínas S100/líquido cefalorraquidiano , Índice de Gravidade de Doença , Adulto JovemAssuntos
Surtos de Doenças/prevenção & controle , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Neisseria meningitidis , África Subsaariana/epidemiologia , Monitoramento Epidemiológico , Humanos , Programas de Imunização/organização & administração , Programas de Imunização/estatística & dados numéricos , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/epidemiologia , Meningite Meningocócica/microbiologia , Neisseria meningitidis/classificação , Neisseria meningitidis/isolamento & purificação , Vacinas Conjugadas/administração & dosagemRESUMO
Recent studies have provided evidence for rapid pathogen genome diversification, some of which could potentially affect the course of disease. We have previously described such variation seen between isolates infecting the blood and cerebrospinal fluid (CSF) of a single patient during a case of bacterial meningitis. Here, we performed whole-genome sequencing of paired isolates from the blood and CSF of 869 meningitis patients to determine whether such variation frequently occurs between these two niches in cases of bacterial meningitis. Using a combination of reference-free variant calling approaches, we show that no genetic adaptation occurs in either invaded niche during bacterial meningitis for two major pathogen species, Streptococcus pneumoniae and Neisseria meningitidis. This study therefore shows that the bacteria capable of causing meningitis are already able to do this upon entering the blood, and no further sequence change is necessary to cross the blood-brain barrier. Our findings place the focus back on bacterial evolution between nasopharyngeal carriage and invasion, or diversity of the host, as likely mechanisms for determining invasiveness.
Assuntos
Adaptação Biológica/genética , Barreira Hematoencefálica/microbiologia , Meningite Meningocócica/microbiologia , Meningite Pneumocócica/microbiologia , Neisseria meningitidis/patogenicidade , Streptococcus pneumoniae/patogenicidade , Portador Sadio/microbiologia , DNA Bacteriano , Variação Genética , Humanos , Meningite Meningocócica/sangue , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Pneumocócica/sangue , Meningite Pneumocócica/líquido cefalorraquidiano , Nasofaringe/microbiologia , Neisseria meningitidis/genética , Streptococcus pneumoniae/genética , Sequenciamento Completo do GenomaRESUMO
Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Haemophilus influenzae type b (Hib) are three most common pathogens accounting for most bacterial meningitis, a serious global infectious disease with high fatality, especially in developing nations. Because the treatment and antibiotics differ among each type, the identification of the exact bacteria causing the disease is vital. Herein, we report a polymer/paper hybrid microfluidic biochip integrated with loop-mediated isothermal amplification (LAMP) for multiplexed instrument-free diagnosis of these three major types of bacterial meningitis, with high sensitivity and specificity. Results can be visually observed by the naked eye or imaged by a smartphone camera under a portable UV light source. Without using any specialized laboratory instrument, the limits of detection of a few DNA copies per LAMP zone for N. meningitidis, S. pneumoniae and Hib were achieved within 1h. In addition, these three types of microorganisms spiked in artificial cerebrospinal fluid (ACSF) were directly detected simultaneously, avoiding cumbersome sample preparation procedures in conventional methods. Compared with the paper-free non-hybrid microfluidic biochip over a period of three months, the hybrid microfluidic biochip was found to have a much longer shelf life. Hence, this rapid, instrument-free and highly sensitive microfluidic approach has great potential for point-of-care (POC) diagnosis of multiple infectious diseases simultaneously, especially in resource-limited settings.
Assuntos
Técnicas Biossensoriais/instrumentação , Haemophilus influenzae/isolamento & purificação , Dispositivos Lab-On-A-Chip , Meningite Meningocócica/diagnóstico , Neisseria meningitidis/isolamento & purificação , Papel , Streptococcus pneumoniae/isolamento & purificação , DNA Bacteriano/análise , DNA Bacteriano/isolamento & purificação , Desenho de Equipamento , Infecções por Haemophilus/líquido cefalorraquidiano , Infecções por Haemophilus/diagnóstico , Infecções por Haemophilus/microbiologia , Humanos , Limite de Detecção , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/microbiologia , Infecções Pneumocócicas/líquido cefalorraquidiano , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/microbiologia , Sistemas Automatizados de Assistência Junto ao Leito , Polímeros/químicaRESUMO
An immunocompetent adult presenting with acellular pneumococcal meningitis is a rare occurrence and may pose a diagnostic challenge.
Assuntos
Ceftriaxona/administração & dosagem , Líquido Cefalorraquidiano/microbiologia , Intervenção Médica Precoce/métodos , Meningite Meningocócica , Streptococcus pneumoniae , Antibacterianos/administração & dosagem , Diagnóstico Diferencial , Diagnóstico Precoce , Feminino , Humanos , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/diagnóstico , Meningite Meningocócica/tratamento farmacológico , Meningite Meningocócica/fisiopatologia , Pessoa de Meia-Idade , Exame Neurológico/métodos , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Resultado do TratamentoRESUMO
A young woman was examined in the Emergency Department for fever, pharyngitis and widespread petechial rash. Physical examination, including neurological evaluation, did not show any other abnormalities. Chest X-ray was negative. Blood exams showed leukocytosis and CPR 20 mg/dL (nv<0.5 mg/dL). On the basis of these results and petechial rash evidence, lumbar puncture was performed. CSF was opalescent; physico-chemical examination showed: total proteins 2.8 (nv 0.15-0.45), glucose 5 (nv 59-80), WBC 7600/µL (nv 0-4/ µL). In the hypothesis of meningococcal meningitis, antimicrobial therapy was started. Blood and cerebrospinal fluid cultures were positive for N. meningitidis. During the first hours the patient experienced hallucinations and mild psychomotor agitation, making a spontaneous recovery. A brain MRI showed minimal extra-axial inflammatory exudates. She was discharged after 10 days in good condition. We underline the need to consider meningococcal meningitis diagnosis when any suggestive symptom or sign is present, even in the absence of the classic meningitis triad, to obtain earlier diagnosis and an improved prognosis.
Assuntos
Febre/etiologia , Meningite Meningocócica/diagnóstico , Neisseria meningitidis/isolamento & purificação , Faringite/etiologia , Púrpura/etiologia , Adulto , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Imagem de Difusão por Ressonância Magnética , Alucinações/etiologia , Humanos , Imunocompetência , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/complicações , Meningite Meningocócica/diagnóstico por imagem , Neuroimagem , Agitação Psicomotora/etiologia , Punção EspinalRESUMO
A highly efficient recognition unit based on surface-enhanced Raman spectroscopy (SERS) was developed as a promising, fast, and sensitive tool for detection of meningococcal meningitis, which is an extremely serious and often fatal disease of the nervous system (an inflammation of the lining around the brain and spinal cord). The results of this study confirmed that there were specific differences in SERS spectra between cerebrospinal fluid (CSF) samples infected by Neisseria meningitidis and the normal CSF, suggesting a potential role for neopterin in meningococcal meningitis detection and screening applications. To estimate the best performance of neopterin as a marker of bacterial infection, principal component analysis (PCA) was performed in a selected region (640-720 cm(-1)) where the most prominent SERS peak at 695 cm(-1) arising from neopterin was observed. The calculated specificity of 95 % and sensitivity of 98 % clearly indicate the effective diagnostic efficiency for differentiation between infected and control samples. Additionally, the limit of detection (LOD) of neopterin in CSF clinical samples was estimated. The level of neopterin was significantly higher in CSF samples infected by N. meningitidis (48 nmol/L), compared to the normal (control) group (4.3 nmol/L). Additionally, this work presents a new type of SERS-active nanostructure, based on polymer mats, that allows simultaneous filtration, immobilization, and enhancement of the Raman signal, enabling detection of spectra from single bacterial cells of N. meningitidis present in CSF samples. This provides a new possibility for fast and easy detection of bacteria in CSF and other clinical body fluids on a time scale of seconds. This method of detection produces consistent results faster and cheaper than traditional laboratory techniques, demonstrates the powerful potential of SERS for detection of disease, and shows the viability of future development in healthcare applications.
Assuntos
Líquido Cefalorraquidiano/química , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/diagnóstico , Neopterina/líquido cefalorraquidiano , Análise Espectral Raman/métodos , Humanos , Limite de Detecção , Meningite Meningocócica/microbiologia , Neisseria meningitidis/genética , Neisseria meningitidis/isolamento & purificação , Neisseria meningitidis/fisiologiaRESUMO
The incidence of invasive infections due to Neisseria meningitidis in Israel is about 1/100 000 population annually. Three cases of meningococcal meningitis were reported in employees at a single plant; the first case appeared in March 2013 and the second and third cases appeared in December, almost 9 months later. N. meningitidis serogroup B was isolated from cerebrospinal fluid samples. Multilocus sequence typing assigned the three meningococcal isolates to ST10418, a new sequence type and a member of the ST32 clonal complex. The clonality was confirmed by performance of pulsed-field gel electrophoresis. Post-exposure antibiotic prophylaxis was administered to close contacts of the first case. Upon the diagnosis of the additional two cases, post-exposure prophylaxis was administered to all the plant employees. This report demonstrates the importance of combining public health measures and advanced laboratory studies to confirm clonality and to prevent further disease spread in a closed setting.
Assuntos
Antibacterianos/uso terapêutico , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/tratamento farmacológico , Neisseria meningitidis Sorogrupo B/genética , Profilaxia Pós-Exposição , Adulto , Análise por Conglomerados , Eletroforese em Gel de Campo Pulsado , Humanos , Israel , Masculino , Meningite Meningocócica/microbiologia , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Neisseria meningitidis Sorogrupo B/isolamento & purificaçãoRESUMO
The degree of phosphorylation and phosphoethanolaminylation of lipid A on neisserial lipooligosaccharide (LOS), a major cell-surface antigen, can be correlated with inflammatory potential and the ability to induce immune tolerance in vitro. On the oligosaccharide of the LOS, the presence of phosphoethanolamine and sialic acid substituents can be correlated with in vitro serum resistance. In this study, we analyzed the structure of the LOS from 40 invasive isolates and 25 isolates from carriers of Neisseria meningitidis without disease. Invasive strains were classified as groups 1-3 that caused meningitis, septicemia without meningitis, and septicemia with meningitis, respectively. Intact LOS was analyzed by high resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Prominent peaks for lipid A fragment ions with three phosphates and one phosphoethanolamine were detected in all LOS analyzed. LOS from groups 2 and 3 had less abundant ions for highly phosphorylated lipid A forms and induced less TNF-α in THP-1 monocytic cells compared with LOS from group 1. Lipid A from all invasive strains was hexaacylated, whereas lipid A of 6/25 carrier strains was pentaacylated. There were fewer O-acetyl groups and more phosphoethanolamine and sialic acid substitutions on the oligosaccharide from invasive compared with carrier isolates. Bioinformatic and genomic analysis of LOS biosynthetic genes indicated significant skewing to specific alleles, dependent on the disease outcome. Our results suggest that variable LOS structures have multifaceted effects on homeostatic innate immune responses that have critical impact on the pathophysiology of meningococcal infections.
Assuntos
Antígenos de Bactérias/toxicidade , Portador Sadio/microbiologia , Lipopolissacarídeos/toxicidade , Meningite Meningocócica/microbiologia , Infecções Meningocócicas/microbiologia , Neisseria meningitidis Sorogrupo B/patogenicidade , Neisseria meningitidis Sorogrupo C/patogenicidade , Acilação , Adolescente , Antígenos de Bactérias/biossíntese , Antígenos de Bactérias/química , Portador Sadio/sangue , Portador Sadio/líquido cefalorraquidiano , Portador Sadio/imunologia , Linhagem Celular Tumoral , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Imunidade Inata/efeitos dos fármacos , Lipopolissacarídeos/biossíntese , Lipopolissacarídeos/química , Meningite Meningocócica/sangue , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/imunologia , Infecções Meningocócicas/sangue , Infecções Meningocócicas/líquido cefalorraquidiano , Infecções Meningocócicas/imunologia , Estrutura Molecular , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/metabolismo , Neisseria meningitidis Sorogrupo B/classificação , Neisseria meningitidis Sorogrupo B/imunologia , Neisseria meningitidis Sorogrupo B/metabolismo , Neisseria meningitidis Sorogrupo C/classificação , Neisseria meningitidis Sorogrupo C/imunologia , Neisseria meningitidis Sorogrupo C/metabolismo , Noruega , Fosforilação , Sepse/sangue , Sepse/líquido cefalorraquidiano , Sepse/imunologia , Sepse/microbiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Fator de Necrose Tumoral alfa/metabolismo , VirulênciaRESUMO
Meningitis necessitates immediate diagnosis and therapy. It is important to distingu- ish bacterial from aseptic meningitis, as this help to avoid complications and unnece- ssary antibiotic use. This work assessed the diagnostic and prognostic role of cerebro-spinal fluid interleukin-8 (IL-8) level in adult patients with meningitis. Ninety adult patients with meningitis were studied. They were divided into 3 groups: bacterial, tuberculous and aseptic meningitis. Full clinical examination and laboratory workup of meningitis were done. Cerebrospinal fluid (CSF) IL-8 levels were assessed. Patients were followed up till discharge or death. CSF IL-8 level was significantly higher in bacterial and tuberculous meningitis in comparison to aseptic meningitis. At cut off value 121.77 pg/ml, the area under ROC curve was 0.774 with efficacy 69% for differentiating viral from non-viral meningitis. The test efficacy is low in differentiating tuberculous from bactedal meningitis. There is no correlation of CSF IL-8 levels and disease severity or prognosis.
Assuntos
Interleucina-8/líquido cefalorraquidiano , Meningite Asséptica/diagnóstico , Meningites Bacterianas/diagnóstico , Tuberculose Meníngea/diagnóstico , Adulto , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Haemophilus influenzae/isolamento & purificação , Humanos , Masculino , Meningite Asséptica/líquido cefalorraquidiano , Meningites Bacterianas/líquido cefalorraquidiano , Meningite por Haemophilus/líquido cefalorraquidiano , Meningite por Haemophilus/diagnóstico , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/diagnóstico , Meningite Pneumocócica/líquido cefalorraquidiano , Meningite Pneumocócica/diagnóstico , Pessoa de Meia-Idade , Neisseria meningitidis/isolamento & purificação , Prognóstico , Curva ROC , Streptococcus pneumoniae/isolamento & purificação , Tuberculose Meníngea/líquido cefalorraquidianoRESUMO
BACKGROUND: Bacterial meningitis is a fatal infectious disease of the central nervous system complicating intravascular involvements. Multiple microbleeds are rarely identified as complications because of the limited detection threshold of conventional imaging modalities. We report the first case of meningococcal meningitis with successful identification of multiple microbleeds in the cerebellum by susceptibility-weighted imaging. CASE PRESENTATION: A 19-year-old Japanese female was brought to our emergency department because of fever and coma. A spinal tap was performed and turbid yellow fluid was collected. A diagnosis of bacterial meningitis was established and the patient was admitted to an intensive care unit. Dexamethasone and Antibiotics were administered and Neisseria meningitides was cultured from the spinal fluid. On day 10, postcontrast magnetic resonance imaging identified enhanced subarachnoid space in the cerebellum. Susceptibility-weighted imaging showed spotty low-intensity signals in the cerebellar tissue, indicating microbleeds. The patient made a full recovery from coma and was discharged without neurological sequelae on day 24. CONCLUSION: Meningococcal meningitis can cause multiple microbleeds in the cerebellum. In this report, we successfully identified microbleeds by susceptibility-weighed imaging. Using this imaging modality, further investigations will clarify its clinical incidence and significance.
Assuntos
Cerebelo/patologia , Hemorragia Cerebral/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Meningite Meningocócica/complicações , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Feminino , Humanos , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/tratamento farmacológico , Meningite Meningocócica/patologia , Adulto JovemRESUMO
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.