Cerebrospinal Fluid Biomarkers of Symptomatic Neurosyphilis in People With HIV Compared with Uninfected Individuals.

We evaluated the diagnostic clinical performance characteristics (DCPC) of cerebrospinal fluid (CSF) total protein (TP), white blood cell count (WBC), and lactate (LA) with different cutoff points as adjunct biomarkers of confirmed or presumptive symptomatic neurosyphilis (NS) and the impact of HIV infection. From 5,640 participants who underwent lumbar punctures, 236 participants were included, and classified as either people with HIV (PWH) or people without HIV (PWoH) according to the CDC criteria for confirmed NS (n = 42), presumptive NS (n = 74), systemic syphilis (SS) (n = 38), serological diagnosis of syphilis (n = 18), PWH without SS and NS (n = 10), and negative control (n = 72). In PWoH, for presumptive NS, the combination of CSF TP > 45 mg/dL and/or WBC > 5.0 cells/mm3 is valuable for screening, whereas in PWH, it is not recommended for either screening or case-finding NS, however the DCPC were better in the suppressed group. In PWoH, the value of CSF TP > 45 mg/dL is adequate for both screening and confirmation of presumptive NS, subject to prevalence. For WBC count > 20 cell/mm3, the positive predictive value (PPV) of the test is almost perfect, suggesting a confirmatory test. In PWH, CSF TP is an inadequate marker of NS. The WBC count, with cutoffs of > 10 or > 20 cells/mm3, was moderately applicable for screening.As conclusions: CSF WBC count and TP showed distinct DCPC in confirmed or presumptive NS, better in the former. These biomarkers could be included for presumptive NS diagnosis. DCPC of these biomarkers for the diagnosis of NS is greatly affected by HIV co-infection.

Comparison between cerebrospinal fluid biomarkers for differential diagnosis of acute meningitis.

OBJECTIVES: Given the difficulty in the differential diagnosis of acute bacterial meningitis (BM) and viral meningitis (VM), we aimed to compare the ability of cerebrospinal fluid (CSF) biomarkers, such as lactate, glucose, lactate dehydrogenase (LDH), C-reactive protein (CRP), total white blood cell count, and predominance of neutrophils, as single tests to differentiate microbiologically defined acute BM and VM. METHODS: CSF samples were divided into three groups: BM (n=17), VM (n=14) (both with the etiological agent identified), and normal control groups (n=26). RESULTS: All the biomarkers studied were significantly higher in the BM group than in the VM or control groups (p>0.05). CSF lactate showed the best diagnostic clinical performance characteristics: sensitivity (94.12%), specificity (100%), positive and negative predictive value (100 and 97.56%, respectively), positive and negative likelihood ratio (38.59 and 0.06, respectively), accuracy (98.25%), and AUC (0.97). CSF CRP is excellent for screening BM and VM, as its best feature is its specificity (100%). CSF LDH is not recommended for screening or case-finding. LDH levels were higher in Gram-negative diplococcus than in Gram-positive diplococcus. Other biomarkers were not different between Gram-positive and negative bacteria. The highest level of agreement between the CSF biomarkers was between CSF lactate and CRP [kappa coefficient, 0.91 (0.79; 1.00)]. CONCLUSIONS: All markers showed significant differences between the studied groups and were increased in acute BM. CSF lactate is better than the other biomarkers studied for screening acute BM due to its high specificity.

Cerebrospinal fluid lactate as a predictive biomarker for tuberculous meningitis diagnosis.

OBJECTIVES: The definitive diagnosis of tuberculous meningitis (TBM) is achieved by identifying Mycobacterium tuberculosis (MTb) in cerebrospinal fluid (CSF); however, diagnostic confirmation is difficult due to the inability of current tests for an effective diagnosis. Our objective was to retrospectively assess the characteristics of CSF lactate (CSF-LA) as an adjunct biomarker in the diagnosis of TBM. METHODS: 608 CSF laboratory reports were assessed. Of these, 560 had clinically suspected TBM. These were classified as definite (n=36), probable (23), possible (278), or non-TBM (223) according to the international consensus TBM case definitions. An additional 48 CSF samples were negative controls with normal CSF. RESULTS: Against a reference standard of definite TBM, the cut-off value for CSF-LA was 4.0 mmol/L, the area under the ROC curve was 0.88 (95% CI, 0.82-0.94; p=0.0001), sensitivity was 69%, specificity 90%, negative predictive value 98%. These diagnostic parameters decreased when calculated against those of the other categories of TBM. CSF-LA exhibited high specificity, efficiency, negative predictive value, and clinical utility index in all the groups studied. CONCLUSIONS: CSF-LA is a useful diagnostic marker to rule out TBM when associated with conventional microbiology tests, nucleic acid amplification assays, and clinical algorithms, particularly in endemic areas.

The Impact of Paracoccidioides spp Infection on Central Nervous System Cell Junctional Complexes.

Paracoccidioidomycosis (PCM), a systemic mycosis caused by the fungus Paracoccidioides spp. is the most prevalent fungal infection among immunocompetent patients in Latin America. The estimated frequency of central nervous system (CNS) involvement among the human immunodeficiency virus (HIV)/PCM-positive population is 2.5%. We aimed to address the impact of neuroparacoccidioidomycosis (NPCM) and HIV/NPCM co-infection on the tight junctions (TJ) and adherens junction (AJ) proteins of the CNS. Four CNS formalin-fixed paraffin-embedded (FFPE) tissue specimens were studied: NPCM, NPCM/HIV co-infection, HIV-positive without opportunistic CNS infection, and normal brain autopsy (negative control). Immunohistochemistry was used to analyze the endothelial cells and astrocytes expressions of TJ markers: claudins (CLDN)-1, -3, -5 and occludin; AJ markers: ß-catenin and E-cadherin; and pericyte marker: alpha-smooth muscle actin. FFPE CNS tissue specimens were analyzed using the immunoperoxidase assay. CLDN-5 expression in the capillaries of the HIV/NPCM coinfected tissues (mixed clinical form of PCM) was lower than that in the capillaries of the HIV or NPCM monoinfected (chronic clinical form of PCM) tissues. A marked decrease in CLDN-5 expression and a compensatory increase in CLDN-1 expression in the NPCM/HIV co-infection tissue samples was observed. The authors suggest that Paracoccidioides spp. crosses the blood-brain barrier through paracellular pathway, owing to the alteration in the CLDN expression, or inside the macrophages (Trojan horse).

Soluble CD14 is subtype-dependent in serum but not in cerebrospinal fluid in people with HIV.

Monocytes and macrophages activation are crucial in human immunodeficiency virus (HIV) central nervous system (CNS) infection and HIV associated neurocognitive disorders (HAND) pathogenesis. The soluble form of CD14 (sCD14) is a marker of monocyte activation. We hypothesized that sCD14 levels would be lower in people with HIV-1 subtype C (HIV-1C) than in HIV-1B owing to a variant Tat cysteine dimotif (C30S31) with reduced chemotactic activity. A total of 68 paired cerebrospinal fluid (CSF) and blood samples from people with HIV (PWH); 27 samples of the HIV-1B subtype and 40 of the non-B HIV-1 subtypes (including 26,HIV-1C), and 18 HIV-negative controls were included. sCD14 levels were quantified using a high-sensitivity enzyme-linked immunosorbent assay. sCD14 increase in serum, but not in CSF, was higher in samples from HIV-1B than HIV-1C (p = 0.002; Cohen's d, 0.7). CSF or serum sCD14 values were not correlated with global deficit score or specific cognitive domains. The impact of HIV-1 on monocyte stimulation biomarkers evaluated by sCD14 in serum was subtype-dependent, higher in HIV-1B than HIV-1C, consistent with reduced chemotactic activity as hypothesized.

Dynamic of humoral response to SARS-CoV-2 anti-Nucleocapsid and Spike proteins after CoronaVac vaccination.

This study aimed to calculate the seroconversion rate and IgG antibody dynamic range of the CoronaVac vaccine in healthcare workers (HCWs) after immunization. Serum samples from 133 HCWs from Southern Brazil were collected 1 day before (Day 0) and +10, +20, +40, + 60, +110 days after administering the vaccine's first dose. Immunoglobulin G (IgG) was quantified using immunoassays for anti-N-protein (nucleocapsid) antibodies (Abbott, Sligo, Ireland) and for anti-S1 (spike) protein antibodies (Euroimmun, Lübeck, Germany). Seroconversion by day 40 occurred in 129 (97%) HCWs for the S1 protein, and in 69 (51.87%) HCWs for the N protein. An absence of IgG antibodies (by both methodologies), occurred in 2 (1.5%) HCWs undergoing semiannual rituximab administration, and also in another 2 (1.5%) HCWs with no apparent reason. This study showed that CoronaVac has a high seroconversion rate when evaluated in an HCW population.

HIV-1C and HIV-1B Tat protein polymorphism in Southern Brazil.

The transactivator of transcription (Tat) is a key HIV regulatory protein. We aimed to identify the frequency of key polymorphisms in HIV-1C compared with HIV-1B Tat protein, chiefly in the cysteine-, arginine-, and glutamine-rich domains and identify novel point mutations in HIV-1B and C sequences from Southern Brazil. This study was the first to investigate the genetic diversity and point mutations within HIV-1 Tat C in a Brazilian cohort. This was an observational, cross-sectional study, which included sequences of HIV-1B (n = 20) and HIV-1C (n = 21) from Southern Brazil. Additionally, 344 HIV-1C sequences were obtained from the Los Alamos database: 29 from Brazil and 315 from Africa, Asia, and Europe. The frequency of C31S substitution on HIV-1 Tat C in Brazil was 82% vs. 10% in the HIV-1B group (p < 0.0001). The frequency of the R57S substitution among the HIV-1C sequences from Brazil was 74% vs. 20% in HIV-1B (p = 0.004), and that of substitution Q63E in HIV-1C was 80% and 20% in HIV-1B (p < 0.0001). The mutation P60Q was more frequent in HIV-1B than in HIV-1C (55% and 6.12%, respectively, p < 0.0001)). Novel point mutations in the HIV-1C and B Tat functional domains were described. The frequency of C31S and other key point mutations in HIV-1 Tat C in Brazil were similar to those described in Africa, although lower than those in India. The Tat-B and C sequences found in Southern Brazil are consistent with biological differences and have potential implications for HIV-1 subtype pathogenesis.

Clinical performance of amperometry compared with enzymatic ultra violet method for lactate quantification in cerebrospinal fluid.

OBJECTIVES: The differential diagnosis between acute bacterial meningitis (BM) and viral meningitis (VM) is crucial for treatment and prognosis. Cerebrospinal fluid (CSF) lactate (LA) is considered a good biomarker for differentiating BM from VM. The objective of this study was to compare the clinical performance of amperometry, which is not validated for measurement of LA in CSF samples, with a validated method (enzymatic ultra violet), for their ability to discriminate between acute BM and VM. METHODS: It was a retrospective, descriptive comparative study, 320 CSF reports were included; LA was quantified in CSF using either Dimension AR machine (Dade Behring) or amperometry (RAPID Point 500, Siemens). All samples with bacteria (n=54) or virus (n=139) identified, compared with a control with normal CSF (n=127). RESULTS: CSF LA levels were comparable for amperometry or enzymatic methods on each group studied, in a wide range of LA levels; it was capable to distinguish BM from VM independent of the method used to quantify. CONCLUSIONS: The findings support the use of the amperometric method in measuring LA concentrations in CSF in a wide range of values. Amperometry is a less expensive method, validated for blood, easily available in small laboratories including in limited resources countries.

Diagnostic characteristics of Xpert MTB/RIF assay for the diagnosis of tuberculous meningitis and rifampicin resistance in Southern Brazil.

BACKGROUND: The timely diagnosis of tuberculous meningitis (TBM) is challenging. Molecular diagnostic tools are necessary for TBM, particularly in low- and middle-income countries. OBJECTIVES: We aimed to calculate the diagnostics characteristics of Xpert MTB/RIF for the detection of Mycobacterium tuberculosis in the cerebrospinal fluid (CSF) and the frequency of rifampicin (RIF)-resistance in the CSF samples. METHODS: A total of 313 consecutive CSF samples were studied and categorized into TBM definite, probable, possible, or not TBM cases based on the clinical, laboratory, and imaging data. RESULTS: For the definite TBM cases (n=7), the sensitivity, specificity, efficiency, and positive likelihood ratio were 100, 97, 97, and 38%, respectively. However, for the TBM definite associated with the probable cases (n=24), the sensitivity decreased to 46%. All CSF samples that were Xpert MTB/RIF-positive were RIF susceptible. CONCLUSION: Xpert MTB/RIF showed high discriminating value among the microbiology-proven TBM cases, although the values for the probable and possible TBM cases were reduced. Xpert MTB/RIF contributes significantly to the diagnosis of TBM, mainly when coupled with the conventional microbiological tests and clinical algorithms.

Diagnostic characteristics of Xpert MTB/RIF assay for the diagnosis of tuberculous meningitis and rifampicin resistance in Southern Brazil / Características diagnósticas do Xpert MTB/RIF para o diagnóstico de meningite tuberculosa e resistência à rifampicina no Sul do Brasil

ABSTRACT Background: The timely diagnosis of tuberculous meningitis (TBM) is challenging. Molecular diagnostic tools are necessary for TBM, particularly in low- and middle-income countries. Objectives: We aimed to calculate the diagnostics characteristics of Xpert MTB/RIF for the detection of Mycobacterium tuberculosis in the cerebrospinal fluid (CSF) and the frequency of rifampicin (RIF)-resistance in the CSF samples. Methods: A total of 313 consecutive CSF samples were studied and categorized into TBM definite, probable, possible, or not TBM cases based on the clinical, laboratory, and imaging data. Results: For the definite TBM cases (n=7), the sensitivity, specificity, efficiency, and positive likelihood ratio were 100, 97, 97, and 38%, respectively. However, for the TBM definite associated with the probable cases (n=24), the sensitivity decreased to 46%. All CSF samples that were Xpert MTB/RIF-positive were RIF susceptible. Conclusion: Xpert MTB/RIF showed high discriminating value among the microbiology-proven TBM cases, although the values for the probable and possible TBM cases were reduced. Xpert MTB/RIF contributes significantly to the diagnosis of TBM, mainly when coupled with the conventional microbiological tests and clinical algorithms.

RESUMO Introdução: O diagnóstico da meningite tuberculosa (TBM) é desafiador. Ferramentas de diagnóstico molecular são necessárias para esse diagnóstico, particularmente em países de baixa e média renda. Objetivos: Calcular as características diagnósticas do Xpert MTB/RIF para a detecção de Mycobacterium tuberculosis no líquido cefalorraquidiano (LCR) e a frequência de resistência à rifampicina (RIF) nas amostras do LCR. Métodos: Um total de 313 amostras consecutivas de LCR foram estudadas e categorizadas em casos de TBM definida, provável, possível ou não TBM, com base nos dados clínicos, laboratoriais e de imagem. Resultados: Para os casos definidos de TBM (n=7), sensibilidade, especificidade, eficiência e razão de verossimilhança positiva foram de 100, 97, 97 e 38%, respectivamente. No entanto, para os casos de TBM definidos associados aos prováveis (n=24), a sensibilidade diminuiu para 46%. Todas as amostras de LCR que foram positivas para Xpert MTB/RIF foram suscetíveis a RIF. Conclusão: O Xpert MTB/RIF mostrou alto valor discriminante entre os casos TBM comprovados por microbiologia, porém o valor nos casos prováveis e possíveis de TBM foram reduzidos. O Xpert MTB/RIF contribui significativamente para o diagnóstico de TBM, principalmente quando associado aos testes microbiológicos convencionais e algoritmos clínicos.

Neurocytoskeleton Proteins in Cerebrospinal Fluid of People With HIV-1 Subtypes B and C.

BACKGROUND: The objective was to compare the effect of HIV-1C and HIV-1B subtypes on neurofilament light (NfL) cerebrospinal fluid (CSF) levels and ratios of NfL to tau proteins. Additional comparisons were performed between people with HIV (PWH), participants with Alzheimer disease (AD), and HIV-negative controls (HIV-). We also calculated the diagnostic characteristics of CSF NfL and its ratios in HIV-associated neurocognitive disorder (HAND) diagnosis. METHODS: CSF NfL, T-tau, and P-tau181 concentrations were measured using immunoassays in a total of 108 CSF samples, including PWH (n = 68), HIV- (n = 16), and participants with AD (n = 24). These proteins were compared between HIV-1B (n = 27) and HIV-1C (n = 26) using multiple linear regression adjusted for nadir CD4 and plasma viral load suppression. Comparisons between PWH, HIV-, and participants with AD were adjusted for gender and age. RESULTS: CSF neurocytoskeleton proteins and their ratios were comparable in HIV-1B and HIV-1C. However, the HIV-1C group had a higher proportion of samples of CSF NfL above the reference value (n = 14, 53.85%) than the HIV-1B group (n = 8, 29.63%), P = 0.098. The values of CSF NfL were higher in the AD group [2578 (1864; 3500) pg/mL] than those in PWH [683 (500; 1197) pg/mL, P < 0.001] and control [660 (539; 802) pg/mL, P = 0.012] groups. The value of CSF NfL and its ratios for HAND diagnosis were poor. CONCLUSION: The effects of HIV-1B and HIV-1C on CSF NfL and tau ratios were comparable. The differences in CSF neurocytoskeleton proteins between PWH and individuals with AD suggested they might not share the same mechanisms of impairment. Further research is necessary to evaluate CSF NfL on the differential diagnoses of HAND with AD.

Cerebrospinal fluid pleocytosis as a predictive factor for CSF and plasma HIV RNA discordance and escape.

The aims of this study were to investigate the frequency of HIV-1 RNA level discordance between the cerebrospinal fluid (CSF) and plasma and of CSF viral escape (CVE) in patients with HIV-1 subtype C on antiretroviral therapy, and evaluate the CSF white blood cell (WBC) performance characteristics in predicting CSF discordance in HIV+ group and the frequency of cognitive impairment in individuals with CSF HIV discordance or escape. HIV-1 RNA levels were assessed in plasma and CSF samples from 68 HIV+ participants without opportunistic infection. CSF discordance was found in 7.4% and CVE in 10%, with comparable frequencies between HIV-1B and C. Twenty samples (29%) showed increased CSF WBC counts. This group had higher CSF and plasma HIV-1 RNA levels than the group with normal WBC counts (p < 0.0001 and 0.006, respectively). The odds of CSF discordance were 18 times higher for a person with CSF WBC count of > 5 cells/mm3 than the group with normal CSF WBC count. CSF WBC counts (cut-off of 15 cells/mm3) showed high-performance characteristics as a predictive biomarker of CSF discordance (AUC the ROC curve 0.98). The frequency of cognitive impairment for CSF escape or discordance was 83% and 80%. The odds of cognitive impairment in these groups were 19 and 15 times higher than those for an HIV(-) person. Viral discordance or escape in the CNS occurs at a comparable frequency for HIV-1C and HIV-1B. The CSF WBC count was effective as a predictive biomarker of CSF and plasma discordance.

Comparison of Cerebrospinal Fluid Biomarkers for Differential Diagnosis of Acute Bacterial and Viral Meningitis with Atypical Cerebrospinal Fluid Characteristics.

OBJECTIVE: Several cerebrospinal fluid (CSF) biomarkers are used to distinguish between acute bacterial meningitis (BM) and viral meningitis (VM). We compared the ability of lactate and glucose (GL) in CSF and the CSF/blood GL ratio to distinguish between acute BM and VM with typical and atypical CSF characteristics. METHODS: Three hundred and twenty-four CSF reports were included, which were distributed as the acute BM, VM, and normal control groups (n = 63, 139, and 122, respectively). RESULTS: Lactate level in the CSF of acute BM group was 4-fold higher than that in the acute VM and control groups (p < 0.0001). CSF lactate presented higher specificity (92%) and negative predictive value (94%) compared to CSF GL and CSF/blood GL ratio in distinguishing acute BM and VM. Definitive acute BM or VM with atypical CSF cell characteristics was observed in 23.2 and 21.6% of samples, respectively, and these groups showed reduced performance of characteristics of all CSF biomarkers. CSF lactate showed better operational characteristics than those of CSF GL and CSF/blood GL ratio, presenting the highest positive likelihood ratio, and thus aided in the differential diagnosis of VM with atypical CSF. CONCLUSION: The CSF lactate assay can be routinely used in laboratories as a rapid, automated, and easy method that is independent of lactate blood levels.

Comparison of cerebrospinal fluid lactate with physical, cytological, and other biochemical characteristics as prognostic factors in acute bacterial meningitis / Comparação do lactato no líquido cefalorraquidiano com as características físicas, citológicas e outros marcadores bioquímicos, como fator prognostico nas meningites bacterianas agudas

ABSTRACT Bacterial meningitis (BM) is associated with a high morbidity and mortality. Cerebrospinal fluid (CSF) lactate may be used as a prognostic marker of this condition. We hypothesized that CSF lactate levels would remain elevated in participants who died of acute BM compared with those who recovered from this disease. Objective: To evaluate the potential use of lactate and other CSF biomarkers as prognostic markers of acute BM outcome. Methods: This retrospective, longitudinal study evaluated dynamic CSF biomarkers in 223 CSF samples from 49 patients who fulfilled the inclusion criteria of acute BM, with bacteria identified by CSF culturing. The participants were grouped according to outcome: death (n = 9; 18.37%) and survival (n = 40; 81.63%). All participants received appropriate antibiotic treatment. Results: In the logistic regression model, lactate concentration in the final CSF sample, xanthochromia, and CSF glucose variation between the first and last CSF samples were predictors of a poor outcome (death). In contrast, decrease in CSF white blood cell count and CSF percentage of neutrophils, increase in the percentage of lymphocytes, and normalization of the CSF lactate concentration in the last CSF sample were predictors of a good prognosis. Conclusion: The study confirmed the initial hypothesis. The longitudinal analysis of CSF lactate is an important predictor of prognosis in acute BM.

RESUMO As meningites bacterianas (MB) estão associadas à alta morbidade e mortalidade. O lactato no líquido cefalorraquidiano (LCR) pode ser usado como biomarcador de prognóstico nas MB. A hipótese desse estudo é que os níveis de lactato no LCR se mantém elevados entre pacientes com MB aguda que evoluem para óbito, ao contrário do que ocorre em pacientes com bom prognóstico. Objetivo: Avaliar o uso potencial do lactato e outros marcadores no LCR como indicador de prognóstico na MB aguda. Métodos: Foi realizado um estudo retrospectivo longitudinal da dinâmica dos biomarcadores bioquímicos, celulares e físicos no LCR. Foram analisadas 223 amostras de 49 pacientes com MB aguda com bactérias identificadas por cultura do LCR. Os participantes foram divididos em dois grupos de acordo com o desfecho: óbito (n = 9; 18,37%) e não óbito (n = 40; 81,63%). Todos os participantes receberam antibioticoterapia adequada. Resultados: No modelo de regressão logística, as variáveis que diferiram significativamente entre os dois grupos foram concentração de lactato na amostra final de LCR, xantocromia e variação da concentração de glicose entre a primeira e a última amostra de LCR. A alteração desses fatores indicou desfechos negativos (óbito), enquanto a diminuição do número de leucócitos e da porcentagem de neutrófilos, assim como a normalização da concentração de lactato no LCR foram preditores de bom prognóstico. Conclusão: O estudo confirmou a hipótese inicial. A análise longitudinal do lactato no LCR é um importante preditor de prognóstico na MB aguda.

Validation of multiplex PCR for the diagnosis of acute bacterial meningitis in culture negative cerebrospinal fluid.

INTRODUCTION: This study evaluated the operational characteristics of the multiplex polymerase chain reaction (PCR) for cerebrospinal fluid (CSF) from patients with cellular and biochemical characteristics of acute bacterial meningitis and positive or negative CSF cultures. METHODS: Multiplex PCR was performed for 36 CSF samples: culture-proven acute bacterial meningitis (n = 7), culture-negative acute bacterial meningitis (n = 17), lymphocytic meningitis (n = 8), and normal CSF (n = 4). The operational characteristics of multiplex PCR were evaluated with definite and probable bacterial meningitis, using culture positive, cytological and biochemical CSF characteristics as the gold standard. RESULTS: Multiplex PCR for CSF was efficient in the group with CSF cellular and biochemical characteristics of acute bacterial meningitis but with a negative CSF culture. This group demonstrated high specificity, positive predictive value, and efficiency. CONCLUSIONS: Multiplex PCR for CSF can improve the speed and accuracy of acute bacterial meningitis diagnosis in a clinical setting as a complement to classical immunological and bacteriological assays in CSF. It is also useful for CSF culture-negative acute bacterial meningitis.

Human adenovirus meningoencephalitis: a 3-years' overview.

Human adenovirus (HAdV) has been recognized as a significant viral pathogen implicated in neurological diseases, particularly in immunocompromised patients. However, its involvement in meningoencephalitis remains unclear. The aim of this study was to investigate HAdV and other viral co-infections in the cerebrospinal fluid (CSF) of patients suspected of having either meningoencephalitis or encephalitis. A total of 373 CSF samples from patients under clinical suspicion of neurological viral infection were included in this study. HAdV was investigated by conventional or multiplex real-time PCR, for different time periods. The frequency of HAdV central nervous system (CNS) infection was 1.08%, predominating in female patients with a predisposing condition, and presented with HAdV encephalitis. HAdV CNS infection was found to occur during the months of autumn and winter. The frequency of HAdV detected in CSF positive samples increased after the change in the diagnostic method from conventional to multiplex real-time PCR. There were no specific NMRI or EEG characteristics and two CSF samples with HAdV encephalitis had normal CSF WBC count. There were two cases of co-infection with HIV; no other co-infections with enterovirus or herpes family viruses were detected. All patients had good outcome. Although HAdV is rarely observable in CNS infectious syndromes, it must be investigated particularly in immunocompromised patients.

Validation of multiplex PCR for the diagnosis of acute bacterial meningitis in culture negative cerebrospinal fluid / Validação do PCR multiplex para o diagnóstico de meningite bacteriana aguda com cultura de liquido cefalorraquidiano negativa

ABSTRACT This study evaluated the operational characteristics of the multiplex polymerase chain reaction (PCR) for cerebrospinal fluid (CSF) from patients with cellular and biochemical characteristics of acute bacterial meningitis and positive or negative CSF cultures. Methods: Multiplex PCR was performed for 36 CSF samples: culture-proven acute bacterial meningitis (n = 7), culture-negative acute bacterial meningitis (n = 17), lymphocytic meningitis (n = 8), and normal CSF (n = 4). The operational characteristics of multiplex PCR were evaluated with definite and probable bacterial meningitis, using culture positive, cytological and biochemical CSF characteristics as the gold standard. Results: Multiplex PCR for CSF was efficient in the group with CSF cellular and biochemical characteristics of acute bacterial meningitis but with a negative CSF culture. This group demonstrated high specificity, positive predictive value, and efficiency. Conclusions: Multiplex PCR for CSF can improve the speed and accuracy of acute bacterial meningitis diagnosis in a clinical setting as a complement to classical immunological and bacteriological assays in CSF. It is also useful for CSF culture-negative acute bacterial meningitis.

RESUMO Este estudo avaliou as características funcionais da reação em cadeia da polimerase (PCR) multiplex para amostras de líquido cefalorraquidiano (LCR) de pacientes com características celulares e bioquímicas de meningite bacteriana aguda e culturas de LCR positivas ou negativas. Métodos: O PCR multiplex foi realizado em 36 amostras de LCR: meningite bacteriana aguda comprovada por cultura (n = 7), meningite bacteriana aguda com cultura negativa (n = 17), meningite linfocítica (n = 8) e LCR normal (n = 4). As características funcionais do PCR multiplex foram avaliadas para meningite bacteriana definitiva e provável, utilizando cultura positiva, características citológicas e bioquímicas do LCR como padrão-ouro. Resultados: O PCR multiplex do LCR foi eficiente no grupo com características celulares e bioquímicas do LCR de meningite bacteriana, mas com cultura do LCR negativa. Este grupo demonstrou especificidade, valor preditivo positivo e eficiência altos. Conclusões: Os autores concluíram que o PCR multiplex do LCR pode melhorar a velocidade e a precisão do diagnóstico de meningite bacteriana em um ambiente clínico como complemento aos ensaios imunológicos e bacteriológicos clássicos no LCR. Também é útil para meningite bacteriana aguda com cultura de LCR negativa.

Diagnostic importance of eosinophilic meningitis in HIV-positive and HIV-negative patients.

The presence of eosinophils in the cerebrospinal fluid (CSF) should always be considered abnormal. This study aimed to evaluate the causes of eosinophils in the CSF of patients who are HIV positive and HIV negative. This is the first study of eosinophils in the CSF of patients who are HIV-positive. This was a retrospective study of CSF reports from 1996 to 2005, patients were selected based on the presence of eosinophils in the CSF. We analyzed 20,008 CSF reports; eosinophils were present in 5%. The median and interquartile range (IQR) of eosinophils was 2% (1%, 4%). Eosinophilic meningitis (CSF eosinophils ≥ 10%) was present in 12% of the samples. The main etiologies were infectious diseases as follows: neurocysticercosis, Cryptococcus sp. meningitis, and acute bacterial meningitis. In HIV-positive cases, all causes were by infectious disease, the main pathogen being Cryptococcus sp. The probability of neurocysticercosis in a patient from an endemic region who is HIV-negative and has CSF eosinophils more than 10% was five times higher compared to a person without eosinophilic meningitis. There was a weak positive correlation between CSF eosinophils and increased serum eosinophils. Among the HIV-negative cases, the most frequent non-infectious causes were cerebrovascular syndromes, of these hemorrhage (91.5%). In the HIV-positive group, there were no cases of non-infectious cerebral disease. CSF eosinophils are suggestive of disease. The causes must be investigated, considering the most prevalent infectious diseases in the region.