Detection and genome characterization of Middelburg virus strains isolated from CSF and whole blood samples of humans with neurological manifestations in South Africa.

BACKGROUND: The Old world Alphavirus, Middelburg virus (MIDV), is not well known and although a few cases associated with animal illness have previously been described from Southern Africa, there has been no investigation into the association of the virus with human illness. The current study aimed to investigate possible association of MIDV infection with febrile or neurological manifestations in hospitalized or symptomatic patients fromGauteng, South Africa. METHODS: This study is a descriptive retrospective and prospective laboratory based study. Archived cerebrospinal fluid (CSF) samples submitted to the National Health Laboratory Service (NHLS), Tshwane Academic division for viral investigation from public sector hospitals in Gauteng as well as EDTA (ethylenediaminetetraacetic acid) whole blood samples from ad hoc cases of veterinary students, presenting with neurological and febrile illness, were selected and screened for the presence of alphaviruses using real-time reverse transcription(rtRT) PCR.Virus isolations from rtRT-PCR positive samples were conducted in Vero cell culture and used to obtain full genome sequences. Basic descriptive statistical analysis was conducted using EpiInfo. RESULTS: MIDV was detected by rtRT-PCR in 3/187 retrospective CSF specimens obtained from the NHLS from hospitalised patients in the Tshwane region of Gauteng and 1/2 EDTA samples submitted in the same year (2017) from ad hoc query arbovirus cases from veterinary students from the Faculty of Veterinary Science University of Pretoria.Full genome sequences were obtained for virus isolates from two cases; one from an EDTA whole blood sample (ad hoc case) and another from a CSF sample (NHLS sample).Two of the four Middelburg virus positive cases,for which clinical information was available, had other comorbidities or infections at the time of infection. CONCLUSION: Detection of MIDV in CSF of patients with neurological manifestations suggests that the virus should be investigated as a human pathogen with the potential of causing or contributing to neurological signs in children and adults.

BAFF serum and CSF levels in patients with multiple sclerosis and infectious nervous system diseases.

PURPOSE: Multiple sclerosis (MS) is the most common immune-mediated CNS disease, characterised by demyelination and progressive neurological disability. The B-cell activating factor BAFF has been described as one important factor in the pathophysiology of different autoimmune diseases. METHODS: We measured BAFF levels in the serum and cerebrospinal fluid (CSF) in 50 consecutive patients with MS and 35 patients with infectious CNS disease (ID). 52 patients with other, non-inflammatory disorders (OND), served as controls. RESULTS: BAFF-serum levels in ID patients were higher than in patients diagnosed with MS (ID 0.55 ± 0.24 ng/ml, MS 0.43 ± 0.14 ng/ml, OND 0.45 ± 0.24 ng/ml; p = 0.09). Interestingly, MS patients had lower BAFF CSF levels compared to the controls and ID patients, and the CSF levels in the latter were elevated compared to those of the controls (MS 0.17 ± 0.11 ng/ml, OND 0.25 ± 0.14 ng/ml, ID 0.97 ± 0.78 ng/ml; p < 0.001). CONCLUSIONS: The ID patients' having higher absolute BAFF levels in the CSF than in the serum indicates that the increased BAFF CSF levels were caused by intrathecal synthesis rather than passive transfer via a disturbed blood-brain-barrier. The significantly decreased BAFF CSF levels in MS patients were a surprising result of our study. Although it has been reported that astrocytes in active MS lesions can express BAFF, the soluble form was not increased in the CSF of MS patients. It remains unclear whether the inflammatory features of active MS plaques are truly represented by the CSF compartment.

Tick-Borne Encephalitis: A Differential Pattern of Intrathecal Humoral Immune Response and Inflammatory Cell Composition Compared with Other Viral CNS Infections.

To investigate whether and how cerebrospinal fluid (CSF) findings can contribute to distinguish tick-borne encephalitis (TBE) from herpes simplex virus (HSV) and varicella zoster virus (VZV) induced central nervous system (CNS) infections (HSV-I, VZV-I). Chart review and identification of TBE, HSV- I, and VZV-I was carried out, fulfilling the following criteria: (1) clinical signs of encephalitis and/or meningitis, (2) complete CSF analysis and confirmed viral etiology by either PCR or antibody testing in CSF, (3) hospitalized patients, and (4) available brain magnetic resonance imaging (MRI). Fifty-nine patients with 118 CSF/serum pairs were included. These comprised 21 with TBE (35 CSF/serum pairs), 20 (40 CSF/serum pairs) with HSV-I, and 18 (43 CSF/serum pairs) with VZV-I. In contrast to HSV-I and VZV-I, CSF cell differentiation in TBE showed more often an increased (>20%) proportion of granulocytes (p < 0.01) and a more frequent quantitative intrathecal IgM synthesis (p = 0.001 and p < 0.01, respectively), while the second was even more pronounced when follow-up CSF analyses were included (p < 0.001). CSF findings help to distinguish TBE from other viral infections. In cases with CSF pleocytosis and a positive history for a stay in or near an endemic area, TBE antibodies in CSF and serum should be determined, especially if granulocytes in CSF cell differentiation and/or an intrathecal IgM synthesis is present.

Interplay between Rapid Diagnostic Tests and Antimicrobial Stewardship Programs among Patients with Bloodstream and Other Severe Infections.

BACKGROUND: Antimicrobial stewardship programs (ASPs) aim to provide optimal antimicrobial therapy to patients quickly to improve the likelihood of overcoming infection while reducing the risk of adverse effects. Rapid diagnostic tests (RDTs) for infectious diseases have become an integral tool for ASPs to achieve these aims. CONTENT: This review explored the demonstrated clinical value of longer-standing technologies and implications of newer RDTs from an antimicrobial stewardship perspective. Based on available literature, the focus was on the use of RDTs in bloodstream infections (BSIs), particularly those that perform organism identification and genotypic resistance detection, phenotypic susceptibility testing, and direct specimen testing. Clinical implications of rapid testing among respiratory, central nervous system, and gastrointestinal infections are also reviewed. SUMMARY: Coupling RDTs with ASPs facilitates the appropriate and timely use of test results, translating into improved patient outcomes through optimization of antimicrobial use. These benefits are best demonstrated in the use of RDT in BSIs. Rapid phenotypic susceptibility testing offers the potential for early pharmacokinetic/pharmacodynamic optimization, and direct specimen testing on blood may allow ASPs to initiate appropriate therapy and/or tailor empiric therapy even sooner than other RDTs. RDTs for respiratory, central nervous system, and gastrointestinal illnesses have also shown significant promise, although more outcome studies are needed to evaluate their full impact.

Blood and cerebrospinal fluid characteristics in neonates with a suspected central nervous system infection.

Clinical signs and symptoms of central nervous system (CNS) infections in neonates are often nonspecific. Therefore, cerebrospinal fluid (CSF) analysis is performed to diagnose CNS infections. Data on combined microbiological results and their correlation with biochemical characteristics in CSF and blood in infants younger than 90 days are limited. This study provides an overview of microbiological test results, CSF- and hematological characteristics among infants with a clinically suspected CNS infection.This retrospective study included infants younger than 90 days, with a clinically suspected CNS infection who underwent a diagnostic lumbar puncture between January 2012 and January 2014. Data on the presence of microbiological pathogens in CSF, CSF inflammation markers (white blood cell [WBC] counts, protein levels and glucose CSF/serum ratio) and blood inflammatory responses (WBC count, C-reactive protein [CRP], neutrophil percentage) were collected by reviewing patient files.We included data from 576 infants (median age 12.5 days, interquartile range, 6-27 days) of whom 383 (66.5%) were born prematurely. In total, 16 bacterial pathogens (3.0%) and 21 viruses (5.5%) were detected in CSF. Escherichia coli was detected in 5 cases (1.0%), Enterovirus was detected in 12 cases (3.1%). Leucocytosis in CSF was associated with identification of a pathogen in CSF. Increased CRP was associated with the identification of a bacterial pathogen in CSF.Bacterial or viral pathogens were only identified in a small proportion of infants with a clinically suspected CNS infection. Leucocytosis in CSF was associated with CNS infection in infants. An increased CRP was indicative of bacterial meningitis.

Utility of Clinical and Laboratory Decision Rules in Identifying Bacterial Meningitis Among Children with Suspicion of Central Nervous System Infections in a Malaria-Endemic Area, Mbarara, Uganda.

Several decision rules combining clinical and biological parameters have been proposed to distinguish bacterial from aseptic meningitis, but have not been evaluated in Africa. In children hospitalized with suspected central nervous system infections in Uganda, we found that the Bacterial Meningitis Score and Meningitest showed lower performance than in European children, and that a decision rule designed specifically using parameters associated with bacterial meningitis also showed inadequate diagnostic performance for clinical use.

High neopterin and IP-10 levels in cerebrospinal fluid are associated with neurotoxic tryptophan metabolites in acute central nervous system infections.

BACKGROUND: The host response to intruders in the central nervous system (CNS) may be beneficial but could also be harmful and responsible for neurologic symptoms and sequelae in CNS infections. This immune response induces the activation of the kynurenine pathway (KP) with the production of neuroactive metabolites. Herein, we explored cytokine and KP responses in cerebrospinal fluid (CSF) and serum in patients with encephalitis, aseptic, and bacterial meningitis. METHODS: Cytokines were measured in CSF and serum by multiplex assay in adult patients with encephalitis of infectious, autoimmune or unknown etiology (n = 10), aseptic meningitis (ASM, n = 25), acute bacterial meningitis (ABM, n = 6), and disease control patients with similar symptoms but without pleocytosis in CSF (n = 42). Liquid chromatography-tandem mass spectrometry (LC-MS/ MS) was used to measure KP metabolites in CSF and serum. RESULTS: A characteristic pattern of increasing cytokine levels and KP metabolites was found in CSF from encephalitis to ASM, with the highest levels in ABM. In ASM and ABM, most inflammatory mediators, including IL-6, IL-8, and IFN-inducible protein-10 (IP-10), showed markedly elevated levels in CSF compared with serum, indicating production within the CNS. In contrast to most mediators, the highest level of IP-10 was found in the ASM group, suggesting a potential role for IP-10 in aseptic/viral meningitis. Neopterin and IP-10 were associated with marked changes in KP metabolites in CSF with increasing kynurenine/tryptophan ratio reflecting indoleamine 2,3-dioxygenase activity. Neopterin, a marker of IFN-γ activity, was associated with an unfavorable balance between neuroprotective and neurotoxic tryptophan metabolites. CONCLUSION: We show that parenchymal and meningeal inflammations in CNS share a characteristic cytokine profile with a general immune response in the CSF with limited influence from the systemic circulation. IFN-γ activity, assessed by neopterin and IP-10 levels, may play a role in the activation of the KP pathway in these patients, potentially mediating neurotoxic effects.

Recommendations for enterovirus diagnostics and characterisation within and beyond Europe.

Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate data on severe EV infections and monitor the circulation of EV types, we have established European non-polio enterovirus network (ENPEN). First task of this cross-border network has been to ensure prompt and adequate diagnosis of these infections in Europe, and hence we present recommendations for non-polio EV detection and typing based on the consensus view of this multidisciplinary team including experts from over 20 European countries. We recommend that respiratory and stool samples in addition to cerebrospinal fluid (CSF) and blood samples are submitted for EV testing from patients with suspected neurological infections. This is vital since viruses like EV-D68 are rarely detectable in CSF or stool samples. Furthermore, reverse transcriptase PCR (RT-PCR) targeting the 5'noncoding regions (5'NCR) should be used for diagnosis of EVs due to their sensitivity, specificity and short turnaround time. Sequencing of the VP1 capsid protein gene is recommended for EV typing; EV typing cannot be based on the 5'NCR sequences due to frequent recombination events and should not rely on virus isolation. Effective and standardized laboratory diagnostics and characterisation of circulating virus strains are the first step towards effective and continuous surveillance activities, which in turn will be used to provide better estimation on EV disease burden.

Population Pharmacokinetics of Combined Intravenous and Local Intrathecal Administration of Meropenem in Aneurysm Patients with Suspected Intracranial Infections After Craniotomy.

BACKGROUND AND OBJECTIVE: For patients with intracranial infection, local intrathecal administration of meropenem may be a useful method to obtain a sufficient drug concentration in the cerebral spinal fluid (CSF). However, a large inter-individual variability may pose treatment efficacy at risk. This study aimed to identify factors affecting drug concentration in the CSF using population pharmacokinetics method. METHODS: After craniotomy, aneurysm patients with an indwelling lumbar cistern drainage tube who received a combined intravenous and intrathecal administration of meropenem for the treatment of suspected intracranial infection were enrolled. Venous blood and CSF specimens were collected for determining meropenem concentrations. Nonlinear mixed-effects modeling method was used to fit blood and CSF concentrations simultaneously and to develop the population pharmacokinetic model. The proposed model was applied to simulate dosage regimens. RESULTS: A three-compartmental model was established to describe meropenem in vivo behavior. Lumbar CSF drainage resulted in a drug loss, and drug clearance in CSF (CLCSF) was employed to describe this. The covariate analysis found that the drainage volume (mL/day) was strongly associated with CLCSF, and the effect of creatinine clearance was significant on the clearance of meropenem in blood (CL). Visual predictive check suggested that the proposed pharmacokinetic model agreed well with the observations. Simulation showed that both intravenous and intrathecal doses should be increased with the increases of minimum inhibitory concentration and daily CSF drainage volume. CONCLUSION: This model incorporates covariates of the creatinine clearance and the drainage volume, and a simple to use dosage regimen table was created to guide clinicians with meropenem dosing.

Neuroinflammation and Infection: Molecular Mechanisms Associated with Dysfunction of Neurovascular Unit.

Neuroinflammation is a complex inflammatory process in the central nervous system, which is sought to play an important defensive role against various pathogens, toxins or factors that induce neurodegeneration. The onset of neurodegenerative diseases and various microbial infections are counted as stimuli that can challenge the host immune system and trigger the development of neuroinflammation. The homeostatic nature of neuroinflammation is essential to maintain the neuroplasticity. Neuroinflammation is regulated by the activity of neuronal, glial, and endothelial cells within the neurovascular unit, which serves as a "platform" for the coordinated action of pro- and anti-inflammatory mechanisms. Production of inflammatory mediators (cytokines, chemokines, reactive oxygen species) by brain resident cells or cells migrating from the peripheral blood, results in the impairment of blood-brain barrier integrity, thereby further affecting the course of local inflammation. In this review, we analyzed the most recent data on the central nervous system inflammation and focused on major mechanisms of neurovascular unit dysfunction caused by neuroinflammation and infections.

Prospective study on the chemokine CXCL13 in neuroborreliosis and other aseptic neuroinfections.

The study evaluates the clinical significance of CXCL13 (leukocyte chemoattractant synthesized in CSF ) in Lyme neuroborreliosis (LNB) and other aseptic CNS infections. 244 patients with symptoms of neuroinfection and/or LNB were divided into groups: A - patients with LNB-positive antibodies in serum and CSF (96) or CSF only (14); B - patients with aseptic non-borrelial neuroinfections (82); C - negative controls (52). Group A was divided into A1-A4 according to pleocytosis in CSF and AIIgG positivity. The highest CSF CXCL13 concentrations (max. 81,287.60pg/ml; median 1766.90pg/ml) were in A1 (positive AI, pleocytosis) and A3 (negative AIIgG, pleocytosis; max. 7201,60pg/ml, median 56.22pg/ml). A2 (positive AI without pleocytosis) and A4 (negative AI without pleocytosis) had low CXCL13 levels - A2 max. 650.50pg/ml (median<7.80pg/ml); A4 max. 118.56pg/ml (median<7.8pg/ml). In B the median was 28.10pg/ml (max. 595.87pg/ml). In C the CXCL13 concentrations were the lowest (max. 83.83pg/ml; median<7.80pg/ml). The lowest cut-off was 29pg/ml (sensitivity 90.0%, specificity 72.2%), the highest one 400pg/ml (sensitivity 59.6%, specificity 94.0%). The group differences of serum CXCL13 were insignificant. The highest concentrations were at the beginning of the disease. In LNB CXCL13 correlates better with the CSF pleocytosis than AI positivity.

SEROPREVALENCE OF TOXOPLASMA GONDII INFECTION AND ITS AS- SOCIATED RISK FACTORS IN NEUROPSYCHIATRIC PATIENTS IN JAZAN PROVINCE, SAUDI ARABIA.

Toxoplasma gondii has worldwide distribution in nearly one-third of the human population. It is a neurotropic protozoan parasite so a potential role of T. gondii infection for some neuropsychiatric disorders was postulated. Patients with psychiatric disorders had high toxoplasmosis se- roprevalence. Limited information about toxoplasmosis seroprevalence in psychiatric patients was known in southern area of Saudi Arabia. The current cross sectional case control study aims at determination of the prevalence of T. gondii IgG & IgM in neuropsychiatric patients in Jazan Province. A total of 162 neuropsychiatric patients from Al-Amal hospital for psychiatric health and 162 subjects without neuropsychiatric manifestations from Jazan General Hospital, Jazan City, KSA. were enrolled in the study. Psychiatric diagnosis was based on the International Classification of Diseases-10 (ICD-10 classification). Serological analysis for latent toxoplasmosis (IgG) and active toxoplasmosis (IgM) was done using Enzyme Linked Immunosorbent Assay (ELISA). Investigations for the association with socio-demographic, clinical and behavioral characteristics in psychiatric patients were also done. The serofrequency of IgG antibodies among neuropsychiatric patients was significantly higher than that of the controls (35.8% vs 14.8%) P = 0.0022. OR 3.2 with 95% CI= (1.4952 to 6.8774). However; serofrequency of toxoplasma IgM antibody between neuro-psychiatric patients and controls was not statistically significant (P > 0.05).,Bivariate and multivariate analysis for socio-demographics and possible associated risk factors showed that contact to cats and/or dogs, eating under cooked meat, and contact to soil were significantly higher in neuropsychiatric patients than controls.

Low plasma C-reactive protein level as an early diagnostic tool for heatstroke vs central nervous system-associated infection in the ED.

PURPOSES: Heatstroke (HS) is a life-threatening condition, manifested by systemic inflammation and multiorgan failure. Rapid recognition and treatment are life saving. We report a laboratory-oriented characterization of HS by low plasma C-reactive protein (CRP) level and propose its usefulness in distinguishing this type of hyperpyrexia from central nervous system-associated high core temperature. METHODS: After institutional review board approval, records of patients admitted to general intensive care unit between August 2008 and September 2011 with core temperature 39.0°C or higher due to HS or meningoencephalitis (ME) were reviewed. Patients' demographics, CRP on admission and 24 to 48 hours later, serum creatinine, creatine phosphokinase, platelets count, international normalized ratio, alanine transaminase, serum pH, and lactate levels were retrieved. RESULTS: Thirty-six patients were admitted to the intensive care unit with high core temperature: 19 patients, aged 21 to 85 years, had HS; 17 individuals, aged 22 to 81 years, had ME. None of the HS individuals had infection. Twelve HS patients were previously healthy; in 13 patients, the event occurred postexercise. Mean admission CRP levels was 2.1 ± 3.3 mg/L in the HS group compared with 129 ± 84 mg/L in the ME patients (P < .0001); mean 24- to 48-hour CRP levels were 14.6 ± 16.8 vs 139 ± 98 mg/L, respectively (P < .0001). There were no clinically significant differences between the groups regarding laboratory parameters indicative of end-organ damage. Six HS patients underwent computed tomography and/or lumbar puncture before starting intensive cooling, due to misdiagnosis; 5 of them died subsequently. CONCLUSIONS: Low serum CRP levels characterize non-central nervous system-associated HS. This available laboratory test could identify noninfectious hyperthermic patients upon admission, saving precious time until treatment and avoiding unnecessary diagnostic tests.

Timing and predictors of fever and infection after craniotomy for epilepsy in children.

BACKGROUND: Fevers and leukocytosis after pediatric craniotomy trigger diagnostic evaluation and antimicrobial therapy for possible brain infection. This study determined the incidence and predictors of infection in infants and children undergoing epilepsy neurosurgery. METHODS: We reviewed the postoperative course of 100 consecutive surgeries for pediatric epilepsy, comparing those with and without infections for clinical variables and daily maximum temperatures, blood white blood cell (WBC) and differential and cerebrospinal fluid (CSF) studies. RESULTS: Infections were the most common adverse events after these surgeries. Four patients (4%) had CSF infections and 12 had non-CSF infections (including 1 with distinct CSF and bloodstream infections). Most (88%) infections occurred before postoperative day 12 and were associated with larger resections involving ventriculostomies. Fevers (T ≥ 38.5°C) were observed in the first 12 days postsurgery in 43% of cases, and were associated with patients undergoing hemispherectomy and multilobar resections. Fevers in the first 3 days postsurgery identified infections with 73% sensitivity, 69% specificity and 70% accuracy; 2 (13%) patients with infections never developed fevers. Peripheral blood WBC >15,000 was found in 49% of patients and 5 cases of infections never had elevated WBC counts. WBC differential, CSF protein, red blood cell, WBC and red blood cell/WBC ratios were poor predictors of infections. Longer hospital stays were associated with infections and hemispherectomy and multilobar resections. Patients with and without infections were equally likely to be seizure free after surgery. CONCLUSIONS: Fevers and elevated blood WBC counts were common after pediatric epilepsy surgery, but CSF infections were uncommon. Positive cultures and other confirmatory microbiologic tests should drive changes in antimicrobial therapy after surgery.

Optimal glycemic control in neurocritical care patients: a systematic review and meta-analysis.

INTRODUCTION: Hyper- and hypoglycemia are strongly associated with adverse outcomes in critical care. Neurologically injured patients are a unique subgroup, where optimal glycemic targets may differ, such that the findings of clinical trials involving heterogeneous critically ill patients may not apply. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing intensive insulin therapy with conventional glycemic control among patients with traumatic brain injury, ischemic or hemorrhagic stroke, anoxic encephalopathy, central nervous system infections or spinal cord injury. RESULTS: Sixteen RCTs, involving 1248 neurocritical care patients, were included. Glycemic targets with intensive insulin ranged from 70-140 mg/dl (3.9-7.8 mmol/L), while conventional protocols aimed to keep glucose levels below 144-300 mg/dl (8.0-16.7 mmol/L). Tight glycemic control had no impact on mortality (RR 0.99; 95% CI 0.83-1.17; p = 0.88), but did result in fewer unfavorable neurological outcomes (RR 0.91; 95% CI 0.84-1.00; p = 0.04). However, improved outcomes were only observed when glucose levels in the conventional glycemic control group were permitted to be relatively high [threshold for insulin administration > 200 mg/dl (> 11.1 mmol/L)], but not with more intermediate glycemic targets [threshold for insulin administration 140-180 mg/dl (7.8-10.0 mmol/L)]. Hypoglycemia was far more common with intensive therapy (RR 3.10; 95% CI 1.54-6.23; p = 0.002), but there was a large degree of heterogeneity in the results of individual trials (Q = 47.9; p<0.0001; I2 = 75%). Mortality was non-significantly higher with intensive insulin in studies where the proportion of patients developing hypoglycemia was large (> 33%) (RR 1.17; 95% CI 0.79-1.75; p = 0.44). CONCLUSIONS: Intensive insulin therapy significantly increases the risk of hypoglycemia and does not influence mortality among neurocritical care patients. Very loose glucose control is associated with worse neurological recovery and should be avoided. These results suggest that intermediate glycemic goals may be most appropriate.

A prospective assessment of the accuracy of commercial IgM ELISAs in diagnosis of Japanese encephalitis virus infections in patients with suspected central nervous system infections in Laos.

Japanese encephalitis virus (JEV) is a major cause of encephalitis in Asia. We estimated the diagnostic accuracy of two anti-JEV immunoglobulin M (IgM) enzyme-linked immunosorbent assays (ELISAs) (Panbio and XCyton JEVCheX) compared with a reference standard (AFRIMS JEV MAC ELISA) in a prospective study of the causes of central nervous system infections in Laos. Cerebrospinal fluid (CSF; 515 patients) and serum samples (182 patients) from those admitted to Mahosot Hospital, Vientiane, were tested. The CSF from 14.5% of acute encephalitis syndrome (AES) patients and 10.1% from those with AES and meningitis were positive for anti-JEV IgM in the reference ELISA. The sensitivities for CSF were 65.4% (95% confidence interval [CI] = 51-78) (Xcyton), 69.2% (95% CI = 55-81) (Panbio), however 96.2% (95% CI = 87-100) with Panbio Ravi criteria. Specificities were 89-100%. For admission sera from AES patients, sensitivities and specificities of the Panbio ELISA were 85.7% (95% CI = 42-100%) and 92.9% (95% CI = 83-98%), respectively.

A case of multidrug resistance in the central nervous system.

HIV-1 infection may persist in the central nervous system (CNS) despite antiretroviral therapy. We present a case of severe cognitive decline in a man with HIV-1 infection on a fully active regimen for five years. All infective causes were excluded. Despite fully suppressed virus in the blood, HIV RNA in the cerebrospinal fluid measured 3.52 log(10) RNA copies/mL and genotyping of this sample showed an extensive pattern of resistance. This suggested that either the antiretroviral agents were not adequately penetrating the CNS or the CNS had resistant virus as a result of adherence problems. This case highlights the possibility that drug-resistant mutations may develop in the CNS compartment while plasma virus remains suppressed.

[Efficacy of cytoflavin in therapy of encephalophathy in patients with neuroinfection].

The use of cytoflavin solution in complex therapy of patients with neuroinfection was studied. It showed a favourable effect on the disease clinical process, evident from less pronounced intoxication and meningeal signs by the 11th day of the treatment and improvement of the liquorological picture. The cytoflavin efficacy was also confirmed by normalization of the brain bioelectric activity evident from the electroencephalograms and by reduction of the level of antioxidants, such as metalloproteids and superoxidodismutase, that was in favour of the drug antiinflammatory and antioxidant effects. The use of cytoflavin tablets during in early convalescence period promoted earlier recovery of the intellectual and mnestic reactions. On the whole, the use of cytoflavin promoted favourable process and outcomes of neuroinfections and could be recommended for the use during the acute state and re habilitation of the patients.