Diagnostic value of heparin-binding protein in the cerebrospinal fluid for purulent meningitis in children

This study aimed to investigate the diagnostic value of heparin-binding protein (HBP) in the cerebrospinal fluid of children with purulent meningitis (PM). This study included 118 children with PM diagnosed at our hospital from January 2018 to January 2020, 110 children with viral meningitis (VM) and 80 children with suspected meningitis who were ruled out by cerebrospinal fluid (CSF) analysis during the same period. HBP and white blood cell (WBC) count in the CSF, and inflammatory factors, including C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and procalcitonin (PCT), were measured. Receiver-operator characteristic curves were used to analyze the predictive value of HBP, CRP, PCT, and TNF-α levels in the diagnosis of PM by CSF analysis. HBP levels in the CSF of children with PM were higher, while the CRP and serum PCT and TNF-α levels were elevated in all groups (P<0.05). In addition, HBP levels in the CSF were more accurate for the diagnosis of PM than traditional diagnostic indexes. HBP levels in the CSF can be used as an important reference for early diagnosis of PM.

Meningitis linfocítica recurrente por virus herpes simple tipo 2 / Recurrent lymphocytic meningitis by herpes simplex virus type 2

La meningitis linfocítica recurrente o meningitis de Mollaret es una entidad asociada a un gran número de etiologías infecciosas, autoinmunes, toxicológicas y neoplásicas. En la actualidad el virus herpes simple tipo 2 (HSV-2) es el agente más frecuentemente aislado. Afecta frecuentemente a mujeres de mediana edad y tiende a autolimitarse sin secuelas dentro de la primera semana de inicio de síntomas. El diagnóstico se basa en la detección de ácidos nucleicos virales en el líquido cefalorraquídeo. Al momento no se ha demostrado beneficio en el uso de tratamiento antiviral en la prevención de recurrencias.

Recurrent lymphocytic meningitis or Mollaret´s meningitis is a rare condition caused by a number of infectious, autoimmune, toxic and neoplastic diseases. Herpes simplex type 2 is the most commonly isolated agent. It usually compromises middle aged women, with a self-limited clinical presentation that resolves within a week leaving no sequelae. Its diagnosis is mainly based on nucleic acid detection on cerebrospinal fluid. Antiviral prophylaxis has not shown conclusive to avoid recurrences.

Two Cases of Uveo-meningeal Syndrome

PURPOSE: We report two cases of uveo-meningeal syndrome involving the retina, uvea, and optic disc in both eyes after viral meningitis. CASE SUMMARY: A 16-year-old female was referred to our department with blurred vision in both eyes. She was hospitalized in the pediatric ward with viral meningitis. She showed a norma best-corrected visual acuity (BCVA) and normal intraocular pressure in both eyes, but had severe inflammation in the anterior chamber on slit lamp examination, and optic disc edema and multiple whitish lesions on fundus examination. She was treated with intravenous antibiotic injections and steroid eye drops. After close observation, inflammation in the anterior chamber, optic disc edema, and the multiple whitish lesions in the retina were improved. A 27-year-old male who was treated for viral meningitis at the neurology department was referred to us with blurred vision in both eyes. His BCVAs were 0.7 (right eye) and 0.6 (left eye). The intraocular pressure was normal in both eyes. Slit lamp examination revealed inflammation in the anterior chamber and optic disc edema, and a fundus examination revealed multiple infiltrations. He received treatment for presumed herpes virus infection. After close observation, inflammation in the anterior chamber, optic disc edema, and multiple infiltrations with hemorrhage in the retina were improved. CONCLUSIONS: Clinicians should consider the possibility of uveo-meningeal syndrome, which can cause inflammation in the uvea,retina, and optic disc simultaneous with viral meningitis accompanying blurred vision.

Cerebrospinal fluid lactate: a differential biomarker for bacterial and viral meningitis in children / Lactato no líquido cefalorraquidiano: um marcador diferencial para meningite bacteriana e meningite viral em crianças

Abstract Objective: To assess the performance of cerebrospinal fluid (CSF) lactate as a biomarker to differentiate bacterial meningitis from viral meningitis in children, and to define an optimal CSF lactate concentration that can be called significant for the differentiation. Methods: Children with clinical findings compatible with meningitis were studied. CSF lactate and other conventional CSF parameters were recorded. Results: At a cut-off value of 3 mmol/L, CSF lactate had a sensitivity of 0.90, specificity of 1.0, positive predictive value of 1.0, and negative predictive value of 0.963, with an accuracy of 0.972. The positive and negative likelihood ratios were 23.6 and 0.1, respectively. When comparing between bacterial and viral meningitis, the area under the curve for CSF lactate was 0.979. Conclusions: The authors concluded that CSF lactate has high sensitivity and specificity in differentiating bacterial from viral meningitis. While at a cut-off value of 3 mmol/L, CSF lactate has high diagnostic accuracy for bacterial meningitis, mean levels in viral meningitis remain essentially below 2 mmol/L.

Resumo Objetivo: Estudar o desempenho do lactato no líquido cefalorraquidiano como biomarcador para diferenciar a meningite bacteriana da meningite viral em crianças, e definir uma concentração de lactato ótima no líquido cefalorraquidiano que possa ser significativa para a diferenciação. Métodos: Foram estudadas crianças com achados clínicos compatíveis com meningite. O nível de lactato no líquido cefalorraquidiano e outros parâmetros convencionais do líquido cefalorraquidiano foram registrados. Resultados: Em um valor de corte de 3 mmol/L, o lactato no líquido cefalorraquidiano apresentou uma sensibilidade de 0,90, especificidade de 1,0, valor preditivo positivo de 1,0, valor preditivo negativo de 0,963, com uma precisão de 0,972. Os índices de probabilidade positivo e negativo foram 23,6 e 0,1, respectivamente. Para comparação entre a meningite bacteriana e viral, a área abaixo da curva do lactato no líquido cefalorraquidiano foi 0,979. Conclusões: Concluímos que o lactato no líquido cefalorraquidiano possui alta sensibilidade e especificidade na diferenciação da meningite bacteriana da meningite viral. Embora em um valor de corte de 3 mmol/L o lactato no líquido cefalorraquidiano possua alta precisão de diagnóstico da meningite bacteriana, os níveis médios na meningite viral permanecem basicamente abaixo de 2 mmol/L.

Varicella Zoster Meningitis in an Immunocompetent Child / 대한소아신경학회지

Neurologic complications associated with varicella zoster virus (VZV) are rare in children. A 13-year-old boy was hospitalized due to headache, fever, and vomiting. Aseptic viral meningitis was strongly suspicious based on findings on physical exam, cerebrospinal fluid examination, and brain magnetic resonance imaging. On the second day of hospitalization, typical zosteriform rashes developed on his left chest wall across the T7-T8 dermatome. Tzanck test of the skin lesion was positive and polymerase chain reaction test for VZV was positive on the second cerebrospinal fluid examination. Serum immunoglobulin levels were within normal range. Intravenous acyclovir was started and symptoms and signs of meningitis gradually improved and the patient was discharged without any complications. In immunocompetent children, VZV meningitis is rare and requires rapid diagnosis and treatment. Therefore, it is necessary to prompt diagnosis and treatment thorough medical history, physical examination and laboratory examination.

A New Scoring System for the Differential Diagnosis between Tuberculous Meningitis and Viral Meningitis

BACKGROUND: Tuberculous meningitis (TBM) is associated with high mortality and morbidity despite administering anti-tuberculous chemotherapy to the patients. Differential diagnosis between TBM and viral meningitis (VM) is difficult in some clinical situations. METHODS: We reviewed and analyzed records of adult patients who were admitted and diagnosed with TBM or VM at a tertiary hospital in Korea, between January 2006 and December 2015. Diagnostic criteria for TBM were categorized into three groups: definite, probable, and possible TBM. The VM group included patients with no evidence of other meningitis who achieved complete recovery with only conservative treatments. Clinical, laboratory and radiological findings, as well as outcomes, were compared between the TBM and VM groups. RESULTS: Ninety-eight patients were enrolled. Among the study patients, 47 had TBM and 51 had VM. Based on univariate analysis and multivariate logistic regression, sodium 70 (U/L) in cerebrospinal fluid (CSF), protein > 160 (mg/dL) in CSF, voiding difficulty, and symptoms of cranial nerve palsy were significant predictive factors for TBM in the final model. We constructed a weighted scoring system with predictive factors from multiple regression analyses. Receiver operating characteristic curve analyses and decision tree analyses were plotted to reveal an optimum cutoff point as 4 with this scoring system (range: 0–13). CONCLUSION: For differential diagnosis between TBM and VM, we created a new weighted scoring system. This scoring system and decision tree analysis are simple and easy to apply in clinical practice to differentiate TBM from VM.

Erythema dyschromicum perstans in a child following an enteroviral meningitis

ABSTRACT A healthy 6-year-old boy presented with an erythematous macular exanthema, meningeal signs and fever, initially diagnosed with probable bacterial meningitis and treated with antibiotic and anti-inflammatory drugs. Enteroviral meningitis was confirmed, but the skin lesions continued to evolve and the patient was ultimately diagnosed with erythema dyschromicum perstans. The boy was followed during three years until the spontaneous resolution of the dermatosis.

Meningitis en el Hospital Nacional: VI muestra nacional de epidemiología / Meningitis in the National Hospital: VI national epidemiological sample

Introducción: las meningitis constituyen un importante problema de Salud Pública, que afectan de manera especial a los niños menores de 5 años. La etiología más frecuente es viral. Desde la introducción de la vacuna conjugada contra H. influenzae tipo b, S. pneumoniae y N. meningitidis los virus pasaron a ser los agentes más frecuentes. A nivel país, en 2014 y 2015, la etiología viral fue la más frecuente con valores de 69% y 77%, respectivamente, atribuyéndose a las bacterianas como segunda causa. Objetivos: describir las características epidemiológicas de las meningitis, en pacientes de todas las edades internados en el lapso de enero del 2014 a octubre del 2015 en el Hospital Nacional de Itauguá, Paraguay. Metodología: estudio epidemiológico, descriptivo, transversal. Se incluye a pacientes de todas las edades que ingresaron con sospecha de meningitis y/o encefalitis en el periodo de estudio. Resultados: en el periodo de estudio ingresaron 173 casos probables de 201 casos sospechosos de meningitis correspondiendo al 0,5% (173/35140) de todos los ingresos hospitalarios. El grupo etario más afectado fue el de menores de 5 años y entre los mayores de 5 años el de 5 a 14 años. En el 53% procedieron del Departamento Central. Los cuadros clínicos fueron: 98 casos (57%) encefalitis viral, meningitis bacteriana aguda 65 casos (37%), 7 casos (4%) meningitis micótica (Criptococcus). Fallecieron 3 casos de encefalitis y 9 casos de meningitis bacteriana aguda. De 25 casos en edad de vacunarse, 52 % se vacunaron para H. influenzae b y 16% contra P. pneumoniae. No se ha registrado vacunación para N. meningitis en ningún caso. Conclusiones: la incidencia total de meningitis en este periodo de estudio fue de 173 casos. Más de la mitad de los casos fueron de etiología viral. La bacteria más frecuentemente identificada fue S. pneumoniae. En general el grupo de edad más afectado fue el de menores de 5 años. La letalidad fue de 3% en los casos de encefalitis viral, 14% en meningitis bacteriana aguda y 43% en meningitis a Criptococcus. Se desconoce el estado de vacunación de casi la mitad de los casos sobre todo de la antineumocóccica.

Introduction: Meningitis is an important public health problem, which affects children under 5 years of age. The most frequent etiology is viral. Since the introduction of the conjugate vaccine against H. b, S. pneumoniae and N. meningitidis, they became the most frequent agents. In the hole country, in 2014 and 2015, the viral etiology was the most frequent with values ​​of 69% and 77%, respectively, being attributed to the bacterial ones as the second cause. Objectives: To know the epidemiological characteristics of meningitis in all ages hospitalized patients from January 2014 to October 2015 at the National Hospital of Itaugua, Paraguay. Methodology: Epidemiological, descriptive, cross-sectional study. Patients of all ages admitted with suspected meningitis and / or encephalitis were included in the study. Results: During the study, 173 probable cases of 201 suspected cases of meningitis corresponding to 0.5% (173/35140) of all hospital admissions were registered. The more affected age group was the group of children under 5 and among patients with more than 5 years, were between 5 to 14 years; In 53%, they came from the central department.98 cases (57%) were viral encephalitis; Acute bacterial meningitis 65 cases (37%); 7 cases (4%) Fungal Meningitis (Cryptococcus). Of 41 confirmed viral cases (42%), 29 cases (71%) were by Enterovirus. 18 cases of MBA were confirmed; S.pneumoniae (8) or Spn, S were identified. Aureus (4), N.meningitidis (2) or NmStreptococcus group B (1), E. coli (1), S. Epidermidis MR (1) and S. agalactiae (1); From 5 Spn the sero types / serogroups were identified: 6C / 6D (1), serotype14 (1), serotype3 (1), NmW 135 (1), Nmsero group B (1) in a young adult case. There were 3 cases of encephalitis and 9 cases of MBA. Twenty-five cases were vaccinated for Hib and 16% were vaccinated against P.pneumoniae; No vaccination has been registered for Nm. Conclusions: The total incidence of meningitis in this period of study was 173 cases. More than half of the cases were of viral etiology; The most frequently identified bacterium was S. pneumoniae. In general, the most affected age group was children under 5 years of age. The majority coming from the Central department and Cordillera. The lethality was 3% in cases of viral encephalitis; 14% in MBA and 43% in Cryptococcus meningitis. It is unknown the vaccination status of almost half of the cases especially of the anti pneumococcal.

A Single Center Study of the Necessity for Routine Lumbar Puncture in Young Infants with Urinary Tract Infection

PURPOSE: Urinary tract infection (UTI) is the most common serious bacterial infection in infants younger than 3 months of age. Lumbar puncture is routinely performed to evaluate febrile young infants for sepsis. However, there is no clear consensus on the use of routine lumbar puncture to diagnose concomitant meningitis in infants with UTI. We evaluated the prevalence of coexisting bacterial meningitis and sterile cerebrospinal fluid (CSF) pleocytosis in young infants with UTI. METHODS: We retrospectively reviewed the medical records of 85 infants with UTI, aged from 29 to 99 days, who were admitted to Daegu Catholic University Medical Center from January 2013 to May 2016. We included 80 patients who had undergone lumbar puncture. Demographic features, clinical features, and laboratory findings were analyzed. Patients were divided into two groups based on the presence of sterile CSF pleocytosis and we compared these groups and assessed the differences between them. RESULTS: Of the 80 UTI patients enrolled, 34 (43%) had sterile CSF pleocytosis. None had bacterial meningitis, and CSF polymerase chain reaction for enterovirus was positive in two patients without CSF pleocytosis. There were no significant differences between the two groups with regards to age, body temperature, peripheral white blood cell count, urinalysis, and duration of hospital stay. CONCLUSIONS: Though sterile CSF pleocytosis is common in young UTI patients, coexisting bacterial or viral meningitis is very rare. Indications for lumbar puncture in these patients depend on clinical condition.

Two Cases of Acute Retinal Necrosis after Viral Meningitis

PURPOSE: To report two cases of acute retinal necrosis following viral meningitis. CASE SUMMARY: A 52-year-old woman who has had viral meningitis presented with visual loss of right eye. Slit-lamp examination showed conjunctival injection and inflammatory cells (2+) in the anterior chamber of the right eye. Funduscopic examination showed multiple yellow-whitish spots in the peripheral retina. Fluorescein fundus angiography showed early hypofluorescence and the late vascular leak in the peripheral retina. After the patient was diagnosed with Acute retinal necrosis (ARN), intravenous acyclovir (2,100 mg/m²/day) was administered. During the treatment period, the retinal detachment of the right eye was found, so the authors performed pars plana vitrectomy. After the surgery, new retinal lesions weren't observed in both eyes during follow-up. A 57-year-old man previously treated with possible viral meningitis presented with visual loss of his right eye. Funduscopic examination showed multiple yellow-whitish spots in the peripheral retina. Fluorescein fundus angiography showed the late vascular leak in the peripheral retina. In the systemic evaluation, Herpes simplex virus and Cytomegalovirus immunoglobulin G were detected. With the impression of ARN, intravenous acyclovir (2,100 mg/m²/day) was administered. No new retinal lesions were observed in both eyes during follow-up. CONCLUSIONS: We report rare cases of ARN occurring after viral meningitis. Uveitis in patients with recent history of meningitis should be examined carefully under the suspicion of ARN.

Clinical Characteristics and Epidemiology of Enteroviral Meningitis Compared to Non-Enteroviral Meningitis in Infants under 3 Months of Age / 이화의대지

OBJECTIVES: To compare the epidemiology, clinical presentation, laboratory findings, seasonality and hospital course of enteroviral meningitis (EM) and non-enteroviral meningitis (NEM) cases in infants under 3 months of age. METHODS: A retrospective chart review was performed of infants under 3 months of age or less with viral meningitis admitted to Ewha Womans University Mokdong Hospital between January 2010 and December 2016. RESULTS: EM patients were more likely to have siblings compared with NEM. Most of EM was diagnosed during the summer season. Almost 80% of EM was diagnosed between July and September. Fever lasted longer in EM patients compared to NEM. White blood cell count (WBC) from the cerebrospinal fluid was higher in EM patients compared with NEM patients. WBC in blood were lower in EM patients compared with NEM patients. C-reactive protein was lower in EM patients compared with NEM patients. Most of the patients were initially started on antibiotics therapy to rule out bacterial meningitis. EM patients received shorter duration of antibiotic treatment compared with NEM patients. CONCLUSION: This study was conducted to augment the understanding of the incidence, epidemiology, transmission in infants, clinical presentation, laboratory findings, seasonality and hospital courses of enteroviral meningitis compared to NEM. Early recognition, rapid diagnosis and proper clinical management can reduce duration of antibiotic treatment.

Red blood cells in cerebrospinal fluid as possible inhibitory factor for enterovirus RT-PCR / Presença de hemácias no líquido cefalorraquidiano como possível fator inibitório da RT-PCR para detecção de enterovirus

ABSTRACT The presence of hemoglobin in samples are considered an important inhibitory factor for polymerase chain reaction (PCR). The aim of this study was to examine the influence of red blood cells (RBC)s in cerebrospinal fluid (CSF) as an inhibitory factor to reverse transcription polymerase chain reaction (RT-PCR) for enteroviruses (EV). Forty-four CSF samples from patients showing characteristics of viral meningitis were assessed for EV by RT-PCR. Viral RNA extracted with guanidine isothyocianate buffer and virus detection was performed by in-house nested PCR. Positivity for EV RT-PCR was higher in CSF samples without RBCs than in samples with RBCs: 13(26%) and 36(9.2%), p = 0.001. In the group with positive EV RT-PCR, the mean + SD CSF RBC was 37 ± 183 cell/mm3; the group with negative results had 580 + 2,890 cell/mm3 (p = 0.007). The acceptable upper limit for CSF RBCs that could not influence RT-PCR was 108 cells/mm3. CSF samples with negative results for EV RT-PCR have more erythrocytes.

RESUMO A presença de hemoglobina em amostras de fluidos corporais é considerada um fator inibitório importante da reação em cadeia da polimerase (PCR). O objetivo deste estudo era examinar a influencia de hemácias no líquido cefalorraquidiano (LCR) como um fator inibitório da RT-PCR para enterovirus (EV). Quatrocentos e quarenta amostras de LCR de pacientes com características de meningite viral foram avaliados para enterovirus por RT-PCR. RNA viral foi extraído com tampão de isotiocianato de guanidina e a detecção viral foi feita com nested PCR in-house. A positividade do EV RT-PCR no LCR foi maior nas amostras de LCR sem hemácias do que as amostras com hemácias: 13 (26%) e 36 (9,2%), respectivamente (p = 0,001). No grupo com resultados EV RT-PCR positivo, a media ± DP do número de hemácias no LCR foi 37 ± 183 cell/mm3 e no grupo com resultados negativos foi 580 ± 2.890 cell/mm3 (p = 0,007). O limite superior aceitável de hemácias no LCR para não inibir o resultado do PCR foi 108 cells/mm3. As amostras de LCR com resultados negativos para RT-PCR EV tem mais eritrócitos em comparação com amostras com resultados positivos.

Parechovirus como agente etiológico de meningitis y/o sepsis viral en lactantes / Parechovirus as etiologic agent of meningitis and/or sepsis like illness in infants

Introduction: Human parechovirus (HPeV) belongs to the Picornaviridae family and has been described in viral meningoencephalitis and sepsis like illness in infants. Until now, 16 genotypes have been recognized, the most common are HPEV 1, 2 and 3; type 3 is most severe. Aims: To estimate the frequency of HPEV etiology in viral meningoencephalitis and sepsis in infants and characterize clinical and molecular aspects of infection. Methods: Between October 2013 and March 2015 we collected CSF samples, plasma, nasopharyngeal swabs and/or stools of patients younger than two years with suspected sepsis and/or viral meningitis. Samples were obtained from laboratory storage sites and from hospitalized patients. HPeV was diagnosed by real-time polymerase chain reaction (PCR) assay against the 5'UTR region. Positive samples were genotyped by sequencing a 304pb segment in VP3/VP1 overlapping region obtained with a nested PCR. Results: Overall HPeV detection rate was 18,6% (11/59 patients), distributed in 8.7% (4/46) laboratory's samples and 53.8% (7/13) of samples from hospitalized patients; mean age was 49 days (SD?). Most common clinical signs were irritability (%), inappetance and fever (algo mas? Magnitude? %). All six samples genotyped were HPeV 3. Conclusions: HPeV should be considered as a relatively significant etiologic agent of viral meningoencephalitis and sepsis in infants.

Introducción: Parechovirus humano (HPeV) pertenece a la familia Picornaviridae; ha sido descrito en sepsis viral y meningoencefalitis en niños de dos años o menos (lactantes). Se conocen 16 genotipos, siendo los más frecuentes HPeV 1, 2 y 3; el más grave es el tipo 3. Objetivos: Estimar la frecuencia de HPeV como agente causal de meningoencefalitis o sepsis viral en lactantes; caracterizar clínica y molecularmente los HPeV encontrados. Material y Métodos: Estudio descriptivo. Se utilizaron muestras de LCR, plasma, hisopado nasofaríngeo y/o deposiciones de lactantes con sospecha de sepsis y/o meningoencefalitis viral entre octubre 2013 y marzo 2015. Se estudiaron muestras almacenadas en laboratorio y de pacientes hospitalizados. Como diagnóstico, se realizó RPC-TR en tiempo real para HPeV dirigido a sector 5'UTR. Para la caracterización molecular, se secuenció un sector de 304 pb en unión VP3/VP1 mediante una RPC-TR anidada. Resultados: Se reclutó un total de 59 pacientes con frecuencia de HPeV de 18,6% (11/59), correspondientes a 8,7% (4/46) en muestras de colección y 53,8% (7/13) en hospitalizados, edad promedio 49 días. En la presentación clínica destacó la irritabilidad, el rechazo alimentario y la fiebre. Seis casos fueron genotipificados, todos correspondieron al tipo HPeV 3. Conclusiones: HPeV debe ser considerado como agente causal en sepsis y/o meningoencefalitis en lactantes.

Avaliação de anticorpos monoclonais como marcadores diferenciais de meningites bacterianas e virais por meio de técnica imuno-histoquímica / Investigation on the monoclonal antibodies as differential markers for viral and bacterial meningitis by means of immnunohistochemistry technique

Desde 1996, o Laboratório de Anticorpos Monoclonais, Antígenos e Adjuvantes - Centro de Imunologia do Instituto Adolfo Lutz (CI-IAL) tem desenvolvido trabalhos na caracterização antigênica de cepas de Neisseria meningitidis utilizando-se painel de anticorpos monoclonais(AcMo) pré-estabelecido, e produção de novos monoclonais para a análise de cepas com perfis desconhecidos. AcMo foram obtidos das diferentes fusões realizadas no laboratórioutilizando-se células esplênicas e linfonodos poplíteos. Dois hibridomas murinos secretores de AcMo anti-N. meningitidis produzidos e caracterizados no CI-IAL têm sido avaliados por meio de estudo imuno-histoquímico (IHQ) no Centro de Patologia-Laboratório de Imunohistoquímica-IAL. Com a padronização da reação, estabeleceu-se um protocolo para efetuar apesquisa de antígenos de N. meningitidis por IHQ. Houve melhoria no diagnóstico histopatológicoda meningite meningocócica, sobretudo em situações em que não há confirmação da presença do microorganismo por técnicas biomoleculares, como PCR, utilizando-se AcMo específicos para antígenos de diferentes sorogrupos, sorotipos e subtipos de N. meningitidis. O resultado obtido nos primeiros testes mostrou-se promissor, e os dois AcMo demonstraram excelentesresultados. Não houve reatividade cruzada com meningite viral, S. pneumoniae, Rickettsia ou rubéola. Nos próximos estudos, é fundamental ampliar número de amostras, incluindo-se aquelas coletadas de pacientes com meningites meningocócicas e de indivíduos infectados com outros agentes patogênicos.

Since 1996, the Laboratory of Monoclonal Antibodies, Antigens and Adjuvants - Immunology Center of the Adolfo Lutz Institute (CI-IAL) has been developing works on the antigenic characterization of strains of Neisseria meningitidis using pre-established panel of monoclonal antibodies (AcMo) And production of new monoclonals for the analysis of strains with unknown profiles. AcMo were obtained from the different fusions performed in the laboratory using splenic and popliteal lymph nodes. Two murine hybridomas secreting anti-N mAb. Meningitidis produced and characterized in CI-IAL have been evaluated by means of an immunohistochemical study (IHC) at the Center for Pathology-Laboratory of Immunohistochemistry-IAL. With the standardization of the reaction, a protocol was established to carry out research of antigens of N. meningitidis by IHC. There was improvement in the histopathological diagnosis of meningococcal meningitis, especially in situations where there is no confirmation of the presence of the microorganism by biomolecular techniques, such as PCR, using specific mAbs specific for antigens of different serogroups, serotypes and subtypes of N. meningitidis. The results obtained in the first tests proved to be promising, and the two MAbs demonstrated excellent results. There was no cross reactivity with viral meningitis, S. pneumoniae, Rickettsia or rubella. In the next studies, it is essential to expand the number of samples, including those collected from patients with meningococcal meningitis and from individuals infected with other pathogens.

Investigation on the monoclonal antibodies as differential markers for viral and bacterial meningitis by means of immnunohistochemistry technique / Avaliação de anticorpos monoclonais como marcadores diferenciais de meningites bacterianas e virais por meio de técnica imuno-histoquímica

Since 1996, the Laboratory of Monoclonal Antibodies Antigens and Adjuvants - Immunology Center of Adolfo Lutz Institute (IC-IAL) has been working on N. meningitidis strains antigens characterization by using a predetermined monoclonal antibodies (MoAb) panel; and the new monoclonal production has been performed for characterizing strains with unknown profiles. MoAb were obtained from different fusions performed at IAL using spleen cells and popliteal lymph nodes. Two murine hybridomas secreting MoAb anti-N. meningitidis antigens, produced and characterized in the Laboratory of IC-IAL, are presently being evaluated by immunohistochemical (IHC) technique at Immunohistochemistry Laboratory - Pathology Center, IAL. After standardizing these reactions, a protocol for performing investigation on N.meningitidis antigens by using IHQ was established. An increment in the histopathological diagnosis of meningococcal meningitis was occurred, by using MoAb specific for antigens from N. meningitidis serogroups, serotypes and subtypes, mainly in those cases without microorganisms confirmation by biomolecular techniques as PCR. The results obtained in these first tests proved to be promising, and two MoAb showed excellent results. No cross-reactivity with viral meningitis, S. pneumoniae, Rickettsia or Rubella was detected. For the further studies, it is fundamental to increase the samples size, including samples from patients with meningococcal meningitis and from individuals infected with other pathogens.

Desde 1996, o Laboratório de Anticorpos Monoclonais, Antígenos e Adjuvantes - Centro de Imunologia do Instituto Adolfo Lutz (CI-IAL) tem desenvolvido trabalhos na caracterização antigênica de cepas de Neisseria meningitidis utilizando-se painel de anticorpos monoclonais (AcMo) pré-estabelecido, e produção de novos monoclonais para a análise de cepas com perfis desconhecidos. AcMo foram obtidos das diferentes fusões realizadas no laboratório utilizando-se células esplênicas e linfonodos poplíteos. Dois hibridomas murinos secretores de AcMo anti-N. meningitidis produzidos e caracterizados no CI-IAL têm sido avaliados por meio de estudo imuno-histoquímico (IHQ) no Centro de Patologia-Laboratório de Imunohistoquímica-IAL. Com a padronização da reação, estabeleceu-se um protocolo para efetuar a pesquisa de antígenos de N. meningitidis por IHQ. Houve melhoria no diagnóstico histopatológico da meningite meningocócica, sobretudo em situações em que não há confirmação da presença do microorganismo por técnicas biomoleculares, como PCR, utilizando-se AcMo específicos para antígenos de diferentes sorogrupos, sorotipos e subtipos de N. meningitidis. O resultado obtido nos primeiros testes mostrou-se promissor, e os dois AcMo demonstraram excelentes resultados. Não houve reatividade cruzada com meningite viral, S. pneumoniae, Rickettsia ou rubéola. Nos próximos estudos, é fundamental ampliar número de amostras, incluindo-se aquelas coletadas de pacientes com meningites meningocócicas e de indivíduos infectados com outros agentes patogênicos.

Avaliação do desempenho da PCR em tempo real para o diagnóstico de meningite por Enterovirus / Evaluation of a real-time PCR assay performance for the diagnosis of enteroviral meningitis

O gênero Enterovirus (EV) é o agente etiológico mais frequente e responsável pela ocorrência de meningite viral no mundo. O objetivo deste trabalho foi de avaliar resultados da implantação do ensaio de PCR em tempo real (RT-qPCR) para a detecção de EV. Foram selecionadas 616 amostras de líquido cefalorraquidiano (LCR) de pacientes com meningite, recebidas para realizar diagnóstico laboratorial no período de 1998-2013. Os RNAs foram extraídos diretamente do LCR pelo método QIAamp®, e o ensaio TaqMan® foi aplicado. A avaliação foi feita comparando-se resultados de RT-qPCR com os obtidos pelo método de isolamento em cultura de células. Das 616 amostras analisadas, 94 (15,2 %) foram positivas para EV no ensaio de RT-qPCR; e na cultura celular EV foi isolado de 58 (9,4 %) amostras. Valores de sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo foram de 89,70 %, 92,40 %, 55,30 % e 98,90 %, respectivamente. O RT-qPCR foi ligeiramente superior à cultura viral para a detecção de EV no LCR. O RT-qPCR TaqMan® é um ensaio rápido e sensível, facilmente exeqüível e com potencial para melhorar o diagnóstico da meningite viral na rotina do laboratório de saúde pública no Estado de São Paulo.

Enterovirus (EV) genus is the most frequent etiological agent causing viral meningitis worldwide. This study aimed at evaluating the performance of real-time reverse transcription-PCR (RT-qPCR) assay for detecting EV. A total of 616 cerebrospinal fluid (CSF) samples from patients with meningitis were selected, among those received at EV diagnosis laboratory from 1998 to 2013. RNAs were directly extracted from CSF by using QIAamp® Viral RNA Mini Kit, and TaqMan® RT-qPCR assay was applied. Evaluation was made by comparing the RT-qPCR results with those found in the cell culture for viral isolation method. Of 616 analyzed samples, 94 (15.20%) were positive for EV RNA on the RT-qPCR assay; and in the cell culture EV was isolated from 58 (9.40 %) samples. The assay showed sensitivity, specificity, positive predictive value and negative predictive value of 89.70 %, 92.40 %, 55.30 % and 98.90 %, respectively. In the present study, the RT-qPCR assay was slightly superior when compared to the viral culture technique for detecting EV from CSF samples. The TaqMan® RT-qPCR assay shows to be a fast and sensitive assay, easy to perform, and it shows a potential to improve the viral meningitis diagnosis in the public health laboratory in São Paulo State.

The usefulness of serum delta neutrophil index for differentiating bacterial and viral meningitis in the emergency department

OBJECTIVE: When managing patients with acute meningitis in an emergency department (ED), early diagnosis of the type of infection (bacterial or viral) considerably affects the clinical course and treatment because of the high mortality and morbidity associated with bacterial meningitis (BM). The serum delta neutrophil index (DNI), a new inflammatory marker, reflects the fraction of circulating immature granulocytes and is elevated in cases of bacterial infection. The objective of this study was to evaluate whether serum DNI can be used to differentiate between BM and viral meningitis (VM) in the ED. METHODS: This retrospective, observational study included 104 consecutive patients (aged >18 years) diagnosed with acute meningitis from January 2012 to November 2014 in a regional emergency center. White blood cell and neutrophil counts, C-reactive protein level, and DNI were evaluated regarding their usefulness for differentiating BM and VM. RESULTS: Serum DNI was not significantly higher in the BM group (n=12) than in the VM group (n=92) (0 [interquartile range, 0% to 2.73%] vs. 0 [interquartile range, 0 to 0%], P=0.057). However, the white blood cell count and C-reactive protein level were statistically higher in the BM group (P=0.034 and P=0.026, respectively). Serum DNI was not found to be a statistically useful differential diagnostic parameter (area under the curve, 0.628; 95% confidence interval, 0.438 to 0.818). CONCLUSION: Currently, there is no evidence that the serum DNI aids in differentiating acute BM from acute VM in the ED.

Factors associated with mumps meningitis and the possible impact of vaccination / 소아과

PURPOSE: Mumps meningitis is a common complication of mumps infection; however, information on mumps meningitis in the postvaccine era is limited. The purpose of the present study was to determine factors associated with mumps meningitis and to discuss the effect of vaccination on this disease. METHODS: We retrospectively reviewed patients younger than 19 years with mumps, diagnosed at a university hospital in Korea between 2003 and 2013. Patients were divided into groups with and without meningitis, and the clinical features of the 2 groups were compared. RESULTS: The study enrolled 119 patients: 19 patients with meningitis and 100 patients without. Univariate analysis showed that older age (median: 15 years vs. 9.5 years, respectively), a longer interval from last vaccination (median: 10.2 years vs. 4.8 years, respectively), and febrile presentation (94.7% vs. 31.0%, respectively) were significantly associated with mumps meningitis. Sex, number of vaccination doses, bilateral parotitis, and the presence of complications other than meningitis did not differ between the 2 groups. In multivariate logistic regression analysis, age (odds ratio, 1.38; 95% confidence interval, 1.01-1.89; P=0.04) and fever (odds ratio, 30.46; 95% confidence interval, 3.27-283.61; P<0.01) remained independent factors for mumps meningitis. CONCLUSION: Clinicians in the postvaccine era should be aware of the possibility of mumps meningitis in febrile cases of mumps in adolescents, regardless of the number of vaccination doses. To establish the role of vaccination in mumps meningitis, further studies will be necessary.

Procalcitonin as a Diagnostic and Prognostic Factor for Tuberculosis Meningitis

BACKGROUND AND PURPOSE: We investigated the potential role of serum procalcitonin in differentiating tuberculosis meningitis from bacterial and viral meningitis, and in predicting the prognosis of tuberculosis meningitis. METHODS: This was a retrospective study of 26 patients with tuberculosis meningitis. In addition, 70 patients with bacterial meningitis and 49 patients with viral meningitis were included as the disease control groups for comparison. The serum procalcitonin level was measured in all patients at admission. Differences in demographic and laboratory data, including the procalcitonin level, were analyzed among the three groups. In addition, we analyzed the predictive factors for a prognosis of tuberculosis meningitis using the Glasgow Coma Scale (GCS) at discharge, and the correlation between the level of procalcitonin and the GCS score at discharge. RESULTS: Multiple logistic regression analysis showed that a low level of procalcitonin (≤1.27 ng/mL) independently distinguished tuberculosis meningitis from bacterial meningitis. The sensitivity and specificity for distinguishing tuberculosis meningitis from bacterial meningitis were 96.2% and 62.9%, respectively. However, the level of procalcitonin in patients with tuberculosis meningitis did not differ significantly from that in patients with viral meningitis. In patients with tuberculosis meningitis, a high level of procalcitonin (>0.4 ng/mL) was a predictor of a poor prognosis, and the level of procalcitonin was negatively correlated with the GCS score at discharge (r=-0.437, p=0.026). CONCLUSIONS: We found that serum procalcitonin is a useful marker for differentiating tuberculosis meningitis from bacterial meningitis and is also valuable for predicting the prognosis of tuberculosis meningitis.

Clinical Characteristics in Herpes Simplex Virus 2 Meningitis in a Retrospective Single Center Study

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is the second most common cause of viral meningitis and the most common cause of recurrent meningitis. Although the incidence of HSV-2 meningitis is high, its clinical characteristics are not well known. The purpose of this study was to review the clinical characteristics and prognosis of HSV-2 meningitis. METHODS: We analyzed patients who were admitted to the Department of Neurology at Severance Hospital with a final diagnosis of HSV-2 meningitis, as confirmed by applying the polymerase chain reaction to the cerebrospinal fluid (CSF) of patients. RESULTS: The study involved 998 patients with aseptic meningitis and 60 patients diagnosed with HSV-2 meningitis. The mean age at meningitis presentation was 32.5 years (range 18-54 years), and 72% of the patients were female. Common clinical symptoms were headache (100%), nausea and/or vomiting (83%), meningismus (57%), and fever (55%). Six patients had a history of genital herpes infection, and 11 had a past history of recurrent meningitis. The CSF study was notable for elevated protein (111.0±53.5 mg/dL, mean±standard deviation) and white cell count (332.0±211.3 cells/µL). The CSF/serum glucose ratio was 0.52±0.90. Various treatments were applied, including conservative care, antiviral agents, empirical antibiotics, and combined treatments. All patients recovered without serious neurologic sequelae. CONCLUSIONS: HSV-2 meningitis is relatively common, as are recurrent episodes. The clinical characteristics of HSV-2 meningitis are similar to those of other types of aseptic meningitis. HSV-2 meningitis is treated using antiviral therapy, and the prognosis is favorable even with conservative treatment.