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Cell-membrane hybrid nanoparticles (NPs) are designed to improve drug delivery, thermal therapy, and immunotherapy for several diseases. Here, we report the development of distinct biomimetic magnetic nanocarriers containing magnetic nanoparticles encapsulated in vesicles and IR780 near-infrared dyes incorporated in the membranes. Distinct cell membranes are investigated, red blood cell (RBC), melanoma (B16F10), and glioblastoma (GL261). Hybrid nanocarriers containing synthetic lipids and a cell membrane are designed. The biomedical applications of several systems are compared. The inorganic nanoparticle consisted of Mn-ferrite nanoparticles with a core diameter of 15 ± 4 nm. TEM images show many multicore nanostructures (∼40 nm), which correlate with the hydrodynamic size. Ultrahigh transverse relaxivity values are reported for the magnetic NPs, 746 mM -1 s -1 , decreasing respectively to 445 mM -1 s -1 and 278 mM -1 s -1 for the B16F10 and GL261 hybrid vesicles. The ratio of relaxivities r 2 / r 1 decreased with the higher encapsulation of NPs and increased for the biomimetic liposomes. Therapeutic temperatures are achieved by both, magnetic nanoparticle hyperthermia and photothermal therapy. Photothermal conversion efficiency ∼25-30% are reported. Cell culture revealed lower wrapping times for the biomimetic vesicles. In vivo experiments with distinct routes of nanoparticle administration were investigated. Intratumoral injection proved the nanoparticle-mediated PTT efficiency. MRI and near-infrared images showed that the nanoparticles accumulate in the tumor after intravenous or intraperitoneal administration. Both routes benefit from MRI-guided PTT and demonstrate the multimodal theranostic applications for cancer therapy.

Background: The intense use of antiretroviral therapy (ART) has reduced morbidity and mortality of HIV infection. In Brazil, the specific contribution of diseases related to HIV infection leading to hospital admission and readmission is not well known., Aims: The study aimed to determine the clinico-epidemiological profile, 30-day readmission rate, and factors associated with this outcome in a cohort of adults with HIV infection in southern Brazil., Methods: Unicentric retrospective cohort, with data collection through the review of medical records and databases., Results: We analyzed 574 index hospitalizations and 451 individuals. Of these, 57.6% were men and the mean (±SD) age was 42.2 ± 12.3 years. Only 43.4% used ART regularly and low CD4 count and high frequency of detectable viral load were observed. HIV/AIDS-related diseases were identified in 55.2%, and tuberculosis was the most frequent etiology leading to index hospitalization. We found a 30-day readmission rate of 11.5% and hospitalization for HIV/AIDS-related illness was associated with a higher risk for the outcome., Conclusions: These findings highlight the need to expand resources for prevention, early diagnosis, retention, and treatment of people living with HIV in the region to reduce HIV/AIDS-associated diseases and possibly minimize consequent hospital readmission of these individuals.

Xpert® MTB/RIF has been widely used for tuberculosis (TB) diagnosis in Brazil, since 2014. This prospective observational study aimed to evaluate the performance of Xpert in different contexts during a two-year period: (i) laboratory and clinical/epidemiological diagnosis; (ii) HIV-positive and -negative populations; (iii) type of specimens: pulmonary and extrapulmonary. Overall, 924 specimens from 743 patients were evaluated. The performance of the assays was evaluated considering culture (Lowenstein Jensen or LJ medium) results and composite reference standard (CRS) classification as gold standard. According to CRS evaluation, 219 cases (29.5%) were classified as positive cases, 157 (21.1%) as 'possible TB', and 367 (49.3%) as 'not TB'. Based on culture, Xpert and AFB smear achieved a sensitivity of 96% and 62%, respectively, while based on CRS, the sensitivities of Xpert, AFB smear, and culture were 40.7%, 20%, and 25%, respectively. The pooled sensitivity and specificity of Xpert were 96% and 94%, respectively. Metric evaluations were similar between pulmonary and extrapulmonary samples against culture, whereas compared to CRS, the sensitivities were 44.6% and 29.3% for the pulmonary and extrapulmonary cases, respectively. The Xpert detected 42/69 (60.9%) patients with confirmed TB and negative culture on LJ medium, and 52/69 (75.4%) patients with negative AFB smear results. There was no significant difference in the diagnostic accuracy based on the types of specimens and population (positive- and negative-HIV). Molecular testing detected 13 cases of TB in culture-negative patients with severe immunosuppression. Resistance to rifampicin was detected in seven samples. Herein, Xpert showed improved detection of pulmonary and extrapulmonary TB cases, both among HIV-positive and -negative patients, even in cases with advanced immunosuppression, thereby performing better than multiple other diagnostic parameters., Competing Interests: The authors have declared that no competing interests exist.

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.

Field observations require adequate metocean data gathering to promote the link between environmental diagnostic and prognostic obtained from modeling techniques. In general, model confidence can be improved by using data which present better quality and by improved parametrizations. This paper discusses and suggests timing routines for data gathering which are enough to describe the hydrodynamic behavior of estuarine and coastal areas. From the environmental diagnostics viewpoint, a sampling procedure is defined to the temporal scales providing data with adequate resolution to describe the natural process without signal aliasing. The proposed sampling procedure was based on the analysis of a data set of tides, currents, waves, water temperature, and meteorological variables observed at several stations along the Brazilian coast. The instrument setup was based mainly on the results of the harmonic analysis of tides. It is shown that the setup of instruments for simultaneous measurements of currents and waves requires special attention particularly in sites that present low currents and the action of waves. A subset of data gathered in shallow bays was used to estimate the surface turbulent stress by using a classical and a slightly modified parametrization for the wind drag coefficient. Under near neutral atmospheric stability conditions and high tide excursion, the surface turbulent stress obtained with the classical and the modified parametrization differed but the current profiles are expected to be only partially affected by wind-induced drift currents.

This study aimed to compare serum amyloid processing biomarkers among HIV subtype B (n = 25), HIV subtype C (n = 26), healthy HIV-negative controls (n = 18), and patients with Alzheimer's disease (AD; n = 24). Immunoassays were used to measure main soluble Aβ isoforms Aβ38, Aβ40, Aβ42, and Aβ-total in serum and cerebrospinal fluid (CSF). People living with HIV (PLWH) and HIV(-) samples, including AD samples, were compared for gender and age, while HIV subtypes were compared for nadir CD4 and plasma viral load suppression. CSF/serum ratios of Aβ40, Aβ42, and Aβ-total were lower in HIV-1C group than in HIV-1B group (p = 0.020, 0.025, and 0.050, respectively). In serum, these biomarkers were comparable. Serum Aβ isoforms were significantly lower in PLWH than in AD. Serum Aβ42 levels in PLWH were decreased compared to those in control group, thus similar to Aβ42 alterations in CSF; these results were different from those observed in AD. Impaired cellular immunity, low CD4 cell count (nadir or current) influences serum Aβ metabolism in HIV-1B but not HIV-1C. However, in PLWH overall, but not in individual HIV subtype groups, greater CD4 recovery, calculated as the difference between current and nadir CD4, correlated with Aβ42/Aβ40 ratio in serum (r s 0.246; p = 0.0479). No significant correlation was found with global deficit score (GDS), an index of neurocognitive performance, age, or duration of infection. These findings are consistent with those of subtype-dependent amyloid processing in blood in chronic HIV disease.

Human immunodeficiency virus (HIV) genetic compartmentalization is defined as genetic differences in HIV in different tissue compartments or subcompartments that characterize viral quasispecies. This descriptive, longitudinal study assessed the dynamics of inflammation, humoral immune response, blood-brain barrier, blood-cerebrospinal fluid (CSF) barrier, as well as neuronal injury biomarkers in serially obtained CSF and serum samples from an antiretroviral (ARV) therapy-naïve patient with HIV-1 subtype C with CSF HIV genetic compartmentalization that resolved spontaneously without ARV treatment. The first CSF sample showed an increase in white blood cell (WBC) count (382 cells/mm 3 ) and a marked increase in the levels of inflammatory cytokines and chemokines, including tumor necrosis factor (TNF)α, interleukin (IL)-10, IP-10, and regulated on activation, normal T cell expressed and secreted (RANTES), which raise the suspicion of dual infection. Serum sample analysis showed all cytokine levels to be normal, with only IP-10 slightly increased. These results corroborate the hypothesis that the CNS immunologic response in a patient with HIV infection was independent of the systemic immunologic response. The patient also had persistently elevated levels of sCD14, neopterin, and β 2 M, which were strongly suggestive of persistent CNS immunologic stimulation. This report describes a patient with HIV subtype C who developed a transient episode of asymptomatic HIV meningitis with compartmentalization of HIV in the CSF that resolved independently of ARV therapy. Extensive CSF studies were performed as part of an ongoing longitudinal study, which revealed CNS immune abnormalities. This case presents evidence of HIV-1 subtype C neurotropism and compartmentalization.

Worldwide, the convergence of tuberculosis (TB) and human immunodeficiency virus type 1 (HIV-1) infection epidemics is a public health challenge. In Brazil, TB is the leading cause of death by infectious disease in people living with HIV (PLWH). This study aimed to report the clinical, demographic, epidemiological, and laboratory data for TB in PLWH. This cross-sectional study involved a retrospective analysis of data for patients with TB/HIV coinfection who attended from 2006 to 2015 through a review of medical records. A total of 182 patients were identified, of whom 12 were excluded. Patients were divided according to whether they had pulmonary tuberculosis (PTB; n = 48; 28%) or extrapulmonary tuberculosis (EPTB; n = 122; 72%). The diagnosis was laboratory confirmed in 75% of PTB patients and 78.7% of EPTB patients. The overall 1-year mortality rate was 37.6%, being 22.9% in PTB patients and 69% in EPTB patients; 84% of these deaths were TB-related. The CD4+ count and disseminated TB were independent risk factors for death. The frequency of resistance among Mycobacterium tuberculosis (MTB) isolates was 14%. TB in PLWH is associated with high morbidity and mortality, and severe immunosuppression is a risk factor for death. Appropriate measures for early TB detection should reduce the case fatality rate in high-burden settings., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Neprilysin (NEP) is the dominant Aβ peptide-degrading enzyme in the brain. HIV-1 subtype B transactivator of transcription protein is known to interfere with NEP function, but whether this is true of HIV-1C transactivator of transcription, which has a defective chemokine motif, is not known. This study aimed to analyze the impact of HIV subtype on NEP-mediated cleavage of Aβ by comparing cerebrospinal fluid (CSF) and serum levels of NEP between HIV+ (27 patients with HIV-1B and 26 with HIV-1C), healthy HIV- controls (n = 13), and patients with Alzheimer disease (n = 24)., Methods: NEP and Aβ oligomers 38, 40, 42 levels were measured in CSF and serum by immunoassays. Ratios between NEP and Aβ-38, 40, 42, and total were calculated in CSF and serum. Comparisons between HIV(+) and HIV(-) were adjusted by linear regression for sex and age; HIV subtype comparisons were adjusted for nadir CD4 and plasma viral load suppression., Results: Levels of NEP and ratios in CSF were comparable for HIV-1C and B subtypes. The ratio of serum NEP/Aβ-40 was lower for HIV1-C than HIV1-B (P = 0.032). The CSF/serum index of NEP/Aβ-40, NEP/Aβ-42, and NEP/Aβ-total were lower for HIV1-B than HIV1-C (P = 0.008, 0.005, and 0.017, respectively), corroborating the findings for serum. CSF NEP was comparable for HIV+, HIV-, and AD., Conclusion: There was impact of HIV subtype on NEP. The ratio of NEP/Aβ-40 on serum was lower on HIV1-C than HIV1-B. These results are consistent with the results of CSF Aβ-42 levels decreased in HIV1-C compared with HIV1-B, suggesting higher amyloid β deposit on HIV1-C than HIV1-B.

Although cognitive impairment has been well documented in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) mono-infections, research on neurocognitive effects is limited in the context of HIV/HCV co-infection. The aims of this study were to explore the interplay between HIV and HCV infections in the expression of neurocognitive impairment (NCI), and to examine the differences in test performance between HIV/HCV co-infected and HIV or HCV mono-infected patients. A total of 128 participants from Southern Brazil underwent a comprehensive neuropsychological (NP) battery comprising 18 tests. Participants were grouped according to their serological status: HCV mono-infected (n = 20), HIV mono-infected (n = 48), HIV/HCV co-infected (n = 12), and HIV-/HCV-uninfected controls (n = 48). The frequencies of HIV subtypes B and C between the HIV mono-infected and HIV/HCV co-infected groups were comparable. There was greater prevalence of neuropsychological impairment among all three infection groups compared with the uninfected control group, but no statistically significant differences among mono- and co-infected groups were found. HCV infection was associated with cognitive deficits, independently of liver dysfunction. HCV infection did not show an additive effect on neurocognitive function among HIV+. NCI was independent of HCV RNA on peripheral blood, CSF, and hepatic injury. While we did not find additive global effect, in the present study, there was some evidence of additive HIV/HCV co-infection effects in speed of information processing, executive function, and verbal fluency domains when comparing the co-infected group with the other three groups. NP impairment was not dependent on HCV subtypes.

Based on prior reports that the HIV-1 Tat protein modulates amyloid-beta (Aβ) metabolism, this study aimed to compare CSF neural injury biomarkers between 27 patients with HIV subtype B, 26 patients with HIV subtype C, 18 healthy HIV-negative controls, and 24 patients with Alzheimer's disease (AD). Immunoassays were used to measure soluble amyloid precursor protein α and β (sAPPα, sAPPβ), Aβ oligomers 38, 40, 42, and Aβ-total; phosphorylated tau (P-tau 181 ), and total tau (T-tau). Comparisons between HIV(+) and HIV(-) (including AD) were adjusted by linear regression for gender and age; HIV subtype comparisons were adjusted for nadir CD4 and plasma viral load suppression. The p values were corrected for multiple testing with the Benjamini-Hochberg procedure. CSF Aβ-42 and Hulstaert (P-tau 181 ) index were lower in HIV1-C than B (p = 0.03, and 0.049 respectively); subtypes did not differ on other CSF biomarkers or ratios. Compared to AD, HIV(+) had lower CSF levels of T-tau, P-tau 181 (p < 0.001), and sAPPα (p = 0.041); HIV(+) had higher CSF Aβ-42 (p = 0.002) and higher CSF indexes: [Aß-42/(240 + 1.18 T-tau)], P-tau 181 /Aβ-42, T-tau/Aβ-42, P-tau 181 /T-tau, sAPPα/β (all p ≤ 0.01) than AD. Compared to HIV(-), HIV(+) had lower CSF Aβ-42, and T-tau (all p ≤ 0.004). As conclusion, amyloid metabolism was influenced by HIV infection in a subtype-dependent manner. Aß-42 levels were lower in HIV1-C than B, suggesting that there may be greater deposition of Aß-42 in HIV1-C. These findings are supported by CSF Hulstaert (P-tau 181 ) index. Differences between HIV and AD in the patterns of Aß and Tau biomarkers suggest that CNS HIV infection and AD may not share some of same mechanisms of neuronal injury.

Combination antiretroviral therapy promotes longer life expectancy, making it possible for perinatally HIV-infected patients to achieve adulthood. Past therapy was not always optimized, suggesting that virological and host features may also play a role in survival. The aim of this study is to describe characteristics of HIV disease progression associated with virological features in adolescents perinatally that were HIV infected. A case series was conducted including 81 patients that were in follow-up at Hospital de Clínicas/Universidade Federal do Paraná, Curitiba, Brazil. Venous blood was collected to conduct tropism and viral subtype assays. The median age was 19 years old (interquartile range 18-21), and a majority of patients were female (54.3%). Viral subtype was obtained for 66 (82%) patients, and subtypes B and C were found in 34% and 59%, respectively. Tropism assay was conducted in 55 (67%) patients: 71% were R5 and 29% X4. Distribution of viral tropism and subtype shows a significant association of subtype C with R5 tropism. Subtype C is more prevalent in southern Brazil and also in the population infected with HIV by vertical transmission. Both R5 tropism and subtype C are associated with slower progression to AIDS. The survival of these patients may be related to virological features present in a benign pattern of disease progression.

Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.

Objectives: The International HIV Dementia Scale (IHDS) was developed to screen for HIV-associated dementia, but it has been used more generally for HIV-associated neurocognitive disorder (HAND). This study sought to examine the accuracy of the IHDS in a cohort of Brazilian HIV-infected individuals and compare its performance to an alternative screening battery for detecting HAND., Methods: A total of 108 participants (including 60 HIV-infected persons) completed the IHDS and a gold standard neuropsychological (NP) battery of 17 tests. As alternative screening method, all possible 3-test combinations from the NP battery were examined and a superiority index (a marker of specificity and sensitivity) was calculated., Results: Sensitivity and specificity to HAND using the standard IHDS cutpoint of 10 were 36% and 75%, respectively. The best balance between sensitivity and specificity was accomplished with a modified cutpoint of 11.5, which yielded sensitivity of 72% and specificity of 58%. The top two most sensitive test combinations, compared with the gold standard NP battery, were Trail Making Test A, Wechsler Adult Intelligence Scale III Digit Symbol and Hopkins Verbal Learning Test-Revised Total Recall (sensitivity 91%, specificity 96%), and Digit Symbol, Brief Visuospatial Memory Test-Revised Total Recall and Grooved Pegboard Test-dominant hand (sensitivity 94%, specificity 91%)., Conclusions: Both test combinations can be administered in less than 10 minutes and were more accurate than the IHDS in classifying HIV+ participants as NP impaired or unimpaired. These data suggest that demographically corrected T-scores from commonly used NP measures with modest time and material demands can improve identification of patients with HAND who may benefit from a more extensive NP examination., Competing Interests: The authors declare that have no conflict of interest.

In Brazil, all patients who fulfill the criteria for AIDS have had free access to antiretroviral therapy since 1996. We performed this cross-sectional study to evaluate the causes of death among 643 HIV-infected patients over three non-consecutive years (2000, 2006, and 2010), using their epidemiological, clinical, and laboratory data. The causes of death were classified as AIDS-defining or non-AIDS-defining conditions. We observed a progressive increase in the prevalence of HIV infection over the study period, although there was also a decrease in the mortality rate for various groups, and especially among pediatric patients. An AIDS-defining condition was recorded as the cause of death for approximately 30% of the patients. There was also a high frequency (>70%) of infectious and parasitic diseases, including opportunistic infections, and the most common diagnoses were septicemia, pneumonia, tuberculosis, and pneumocystosis. Acute respiratory failure was the underlying cause of death in 30% of these cases. Despite advances in HIV therapy, the mortality rate remains high in Brazil. As few Brazilian studies have investigated HIV/AIDS-related mortality, it is important to evaluate and improve the mortality notification databases, in order to provide information regarding the effects of HIV and to guide the implementation of appropriate healthcare measures.

HIV infection is persistent in the CNS, to evaluate the compartmentalization of the CNS immune response to HIV, we compared soluble markers of cellular immunity in the blood and CSF among HIV- (n=19) and HIV+ (n=68), as well as among HIV participants with or without CSF pleocytosis. Dysfunction of the blood cerebrospinal fluid barrier (BCSFB) was common in HIV participants. CSF levels of TNFα, IFNγ, IL-2, IL-6, IL-7, IL-10, IP-10, MIP-1α, MIP-1β, and RANTES were significantly higher in participants with CSF pleocytosis (P<0.05); serum levels of these biomarkers were comparable. The CNS immune response is compartmentalized, and remains so despite the BCSFB dysfunction during HIV infection; it is markedly reduced by virology suppression, although BCSFB dysfunction persists on this subgroup., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A defective chemokine motif in the HIV-1 Tat protein has been hypothesized to alter central nervous system cellular trafficking and inflammation, rendering HIV-1 subtype C less neuropathogenic than B. To evaluate this hypothesis, we compared biomarkers of cellular chemotaxis and inflammation in cerebrospinal fluid (CSF) and serum in individuals infected with HIV-1 subtypes B (n = 27) and C (n = 25) from Curitiba, Brazil. None had opportunistic infections. Chemokines (MCP-1, MIP-1α, MIP-1β, RANTES, IP-10) and cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-10) were measured using the multiplex bead suspension array immunoassays or ELISA HD. CSF and serum biomarker concentrations were compared between subtype B and C groups and HIV-positive and HIV-negative subjects (N = 19) using an independent group t test (unadjusted analysis) and linear regression (adjusted analysis), controlling for nadir CD4 and CSF and plasma HIV RNA suppression. CSF levels of cytokines and chemokines were significantly (p < 0.05) elevated in HIV-positive versus HIV-negative participants for 7/13 biomarkers measured, but levels did not differ for subtypes B and C. Serum levels were significantly elevated for 4/13 markers, with no significant differences between subtypes B and C. Although pleocytosis was much more frequent in HIV-positive than in HIV-negative individuals (27 vs. 0 %), subtypes B and C did not differ (32 and 22 %; p = 0.23). We did not find molecular evidence to support the hypothesis that intrathecal chemotaxis and inflammation is less in HIV-1 subtype C than in subtype B. Biomarker changes in CSF were more robust than in serum, suggesting compartmentalization of the immunological response to HIV., Competing Interests: SERGIO M. DE ALMEIDA , the author declare that have no conflict of interest. YANXIN JIANG , the author declare that have no conflict of interest. INDIANARA ROTTA, the author declare that have no conflict of interest. XIAO LI , the author declare that have no conflict of interest. SONIA M. RABONI , the author declare that have no conflict of interest. CLEA E. RIBEIRO , the author declare that have no conflict of interest. DAVEY SMITH , the author declare that have no conflict of interest. MICHAEL POTTER , the author declare that have no conflict of interest. FLORIN VAIDA , the author declare that have no conflict of interest. SCOTT LETENDRE , the author declare that have no conflict of interest. RONALD J. ELLIS , the author declare that have no conflict of interest.

Major depressive disorder (MDD) is among the most prevalent neuropsychiatric disorders associated with HIV infection; however, its risks and neurobiologic correlates in diverse cultures are poorly understood. This study aimed to examine the frequency of MDD among HIV+ participants in southern Brazil. We hypothesized that the frequency and severity of MDD would be higher among individuals with HIV+ compared with HIV- and higher in HIV subtype B compared with C. Individuals with HIV (n = 39) as well as seronegative controls (n = 22) were enrolled in a cross-sectional, prospective, observational study. Current and lifetime history of MDD was diagnosed by MINI-Plus; symptom severity was assessed by Beck Depression Inventory-II (BDI-II). Current and past episodes of MDD were significantly more frequent in the HIV+ versus HIV- group: current MDD, 15 (38.5 %) vs. 0 (0 %), p = 0.0004; past MDD, 24 (61.5 %) vs. 3 (13.6 %), p = 0.0004. The median BDI-II score in the HIV+ group was significantly higher than that in the HIV- (13 (8-27.5) vs. 2.5 (1-5.5); p < 0.0001). Current suicide risk, defined as during the last month, was found in 18 % of participants in the HIV-positive and none in the HIV-negative group. Neither current MDD frequency (8 (57.1 %) vs. 6 (40 %), p = 0.47) nor BDI-II score differed across subtypes B and C. HIV+ group may be more likely to experience current MDD than HIV-. This was the first study to compare the frequency and severity of MDD in HIV subtypes B and C; we found no difference between HIV subtypes B and C., Competing Interests: SERGIO M. DE ALMEIDA, the author declare that have no conflict of interest. FRANCISCO JAIME BARBOSA, the author declare that have no conflict of interest. RUJVI KAMAT, the author declare that have no conflict of interest. ANA PAULA DE PEREIRA, the author declare that have no conflict of interest. SONIA M. RABONI, the author declare that have no conflict of interest. INDIANARA ROTTA, the author declare that have no conflict of interest. CLEA E. RIBEIRO, the author declare that have no conflict of interest. MARIANA CHERNER, the author declare that have no conflict of interest. RONALD J. ELLIS, the author declare that have no conflict of interest. JOSEPH HAMPTON ATKINSON, the author declare that have no conflict of interest.

Objective: To estimate HIV incidence in two Brazilian municipalities, Recife and Curitiba, in the year of 2013., Methods: The method for estimating incidence was based on primary information, resulting from the Lag-Avidity laboratory test for detection of recent HIV infections, applied in a sample of the cases diagnosed in the two cities in 2013. For the estimation of the HIV incidence for the total population of the cities, the recent infections detected in the research were annualized and weighted by the inverse of the probability of HIV testing in 2013 among the infected and not diagnosed cases. After estimating HIV incidence for the total population, the incidence rates were estimated by sex, age group, and exposure category., Results: In Recife, 902 individuals aged 13 years and older were diagnosed with HIV infection. From these, 528 were included in the study, and the estimated proportion of recent infections was 13.1%. In Curitiba, 1,013 people aged 13 years and older were diagnosed, 497 participated in the study, and the proportion of recent infections was 10.5%. In Recife, the estimated incidence rate was 53.1/100,000 inhabitants of 13 years and older, while in Curitiba, it was 41.1/100,000, with male-to-female ratio of 3.5 and 2.4, respectively. We observed high rates of HIV incidence among men who have sex with men, of 1.47% in Recife and 0.92% in Curitiba., Conclusions: The results obtained in the two cities showed that the group of men who have sex with men are disproportionately subject to a greater risk of new infections, and indicate that strategies to control the spread of the epidemic in this population subgroup are essential and urgent., Objetivo: Estimar a incidência de HIV em dois municípios brasileiros, Recife e Curitiba, no ano de 2013., Métodos: O método de estimação da incidência foi baseado em informações primárias, resultantes do ensaio laboratorial Lag-Avidity para detecção de infecções recentes do HIV, aplicado em uma amostra dos casos diagnosticados nas duas cidades em 2013. Para a estimação da incidência de HIV para a população total das cidades, as infecções recentes detectadas na pesquisa foram anualizadas e ponderadas pelo inverso da probabilidade de teste de HIV no ano de 2013 entre os casos infectados e não diagnosticados. Após a estimação da incidência de HIV para a população total, foram estimadas as taxas de incidência por sexo, faixa de idade e categoria de exposição., Resultados: Em Recife, foram diagnosticados 902 indivíduos de 13 anos e mais com infecção de HIV. Desses, 528 foram incluídos no estudo, e a proporção estimada de infecções recentes foi de 13,1%. Em Curitiba, foram diagnosticadas 1.013 pessoas de 13 anos e mais, 497 participaram do estudo, e a proporção de infecções recentes foi de 10,5%. Em Recife, a taxa de incidência estimada foi de 53,1 por 100 mil habitantes de 13 anos e mais, enquanto em Curitiba, de 41,1 por 100 mil, com razão do sexo masculino para o feminino de 3,5 e 2,4, respectivamente. Foram evidenciadas elevadas taxas de incidência de HIV entre homens que fazem sexo com homens, de 1,47% em Recife e 0,92% em Curitiba., Conclusões: Os resultados obtidos nas duas cidades mostraram que o grupo dos homens que fazem sexo com homens está desproporcionalmente sujeito ao maior risco de novas infecções, e indicam que estratégias para controle da disseminação da epidemia nesse subgrupo populacional são essenciais e urgentes., Competing Interests: The authors declare no conflict of interest.

Objective: The present study was aimed at evaluating the viability of replacing (18)F with (99m)Tc in dose calibrator linearity testing., Materials and Methods: The test was performed with sources of (99m)Tc (62 GBq) and (18)F (12 GBq) whose activities were measured up to values lower than 1 MBq. Ratios and deviations between experimental and theoretical (99m)Tc and (18)F sources activities were calculated and subsequently compared., Results: Mean deviations between experimental and theoretical (99m)Tc and (18)F sources activities were 0.56 (± 1.79)% and 0.92 (± 1.19)%, respectively. The mean ratio between activities indicated by the device for the (99m)Tc source as measured with the equipment pre-calibrated to measure (99m)Tc and (18)F was 3.42 (± 0.06), and for the (18)F source this ratio was 3.39 (± 0.05), values considered constant over the measurement time., Conclusion: The results of the linearity test using (99m)Tc were compatible with those obtained with the (18)F source, indicating the viability of utilizing both radioisotopes in dose calibrator linearity testing. Such information in association with the high potential of radiation exposure and costs involved in (18)F acquisition suggest (99m)Tc as the element of choice to perform dose calibrator linearity tests in centers that use (18)F, without any detriment to the procedure as well as to the quality of the nuclear medicine service.

Blood plasma specimens are the clinical standard for HIV-1 pol gene genotyping from viral populations; however, it is not always successful, often from low viral loads or the presence of polymerase chain reaction (PCR) inhibitors. Objective To describe the successful of HIV-1 genotyping in two samples of cerebrospinal fluid (CSF), after genotype procedures failed from blood. Method Two HIV-infected patients enrolled in a neurocognitive research study were evaluated when standard HIV-1 genotyping failed from blood plasma samples. Genotyping was performed using the commercial system TRUGENE HIV-1 Genotyping Kit and the OpenGene DNA Sequencing System (Siemens Healthcare Diagnostics, Tarrytown, NY, USA). Results CSF genotyping was performed via the same commercial platform and was successful in both cases. Conclusion This report demonstrates that CSF could be used as an alternate clinical specimen for HIV-1 genotyping when it fails from blood.

HIV-1 clade C isolates show reduced Tat protein chemoattractant activity compared with clade B. This might influence neuropathogenesis by altering trafficking of monocytes into the CNS. A previous study suggested low rates of HIV-associated dementia in clade C-infected individuals. The present study evaluated neurocognitive impairment rates in clade B- and C-infected individuals from the same local population. HIV+ and HIV- participants were recruited from the same geographic region in Southern Brazil. We evaluated neuropsychological (NP) impairment using a screening instrument (the International HIV Dementia Scale (IHDS)), as well as a Brazilian Portuguese adaptation of a comprehensive battery that has demonstrated sensitivity to HIV-associated neurocognitive disorders (HAND) internationally. NP performance in controls was used to generate T scores and impairment ratings by the global deficit score (GDS) method. Clade assignments were ascertained by sequencing pol and env. Blood and cerebrospinal fluid were collected from all HIV+ participants. HIV+ and HIV- participants were comparable on demographic characteristics. HIV+ participants overall were more likely to be impaired than HIV- by the IHDS and the GDS. Clade B- and C-infected individuals were demographically similar and did not differ significantly in rates of impairment. The prevalence of pleocytosis, a marker of intrathecal cellular chemotaxis, also did not differ between clade B and C infections. Clade B and C HIV-infected individuals from the same geographic region, when ascertained using comparable methods, did not differ in their rates of neurocognitive impairment, and there was no evidence of differences in CNS chemotaxis.

Background: Brazil accounts for the largest number of HIV+ persons in Latin America, and this epidemic poses a significant public health burden in this country. Little is known about the neuropsychiatric and functional consequences of HIV infection in this population., Methods: Participants were 43 HIV+ and 29 HIV- individuals who underwent a neuropsychological, psychiatric and neurological evaluation that included self-report measures of mood (Beck Depression Inventory-II; BDI-II), neurocognitive complaints (Patient's Assessment of Own Functioning Inventory) and declines in instrumental activities of daily living (Activities of Daily Living questionnaire). The MINI-Plus generated major depressive disorder (MDD) diagnoses. Apathy, defined as social withdrawal, decision-making difficulty, loss of interest and pleasure, was measured using items from the BDI-II and the neurological evaluation., Results: When compared with seronegative participants, HIV+ individuals endorsed higher levels of apathy spectrum symptoms. After adjusting for mood and other covariates, apathy significantly predicted worse everyday functioning., Limitations: The small sample size, along with the self-report measures used to evaluate apathy and functional difficulties limit the inferences that may be drawn from our findings., Conclusions: Our Brazilian HIV+ cohort endorsed apathy and depression as well as significant functional complaints. Although correlated with depression, apathy was uniquely associated with functional difficulties. Clinical attention to apathy and depression in HIV-infected Brazilians may help identify patients at risk for functional difficulties who may benefit from additional support to maintain independence., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Introduction: Fibromyalgia syndrome (FS) is a common painful condition of the musculoskeletal system that is typically accompanied by several symptoms in other systems. In Brazil, the prevalence of FS is estimated at 2.5%. Here, we present the initial data from Epi-Fibro, a nationwide databank of FS patients seen in public and private settings., Objective: The aims of this study were to assess how the diagnosis of FS was made, identify a set of clinical domains considered relevant by both clinicians and patients in cases of FS, analyse the impact of disease on patient quality of life, and compare the findings among patients of public and private services., Methods: Based on the results of questionnaires, we analysed data corresponding to the first 500 women in the database. Questionnaires pertaining to demographic and clinical data and the Fibromyalgia Impact Questionnaire (FIQ), which was translated and validated for Brazilian patients, were completed by the clinicians and/or patients., Results: Preliminary analysis of the EpiFibro databank revealed that female FS patients in Brazil reported a high impact of disease, as measured by the FIQ, a high prevalence of associated symptoms, and a low degree of education (consistent with the public health care in Brazil used mainly by the underserved). In addition, most patients perceived their pain as diffuse from the onset of disease., Conclusion: Depression and anxiety were seen as the main triggers of FM symptoms, but a significant proportion of the subjects perceived work strain as the initial trigger.We also observed a delay of a few years in seeking medical help and examination by a rheumatologist.

Objective: Compare the characteristics of AIDS patients and treatment outcomes under three different antiretroviral treatment regimens advocated by the Ministry of Health of Brazil., Methods: Retrospective cohorts of patients who had survived up to five years after diagnosis were constructed. The data were obtained from medical records, medication dispensing forms, and death certificates of patients in Curitiba, in the Brazilian state of Paraná. Six hundred patients were selected from the first six months following the adoption of each of the treatment regimens (1992, 1997, and 2002)., Results: The ratio of men to women fell from 6.5:1 in 1992 to 1.4:1 in 2002. There was a proportionate rise in the number of people over 50, which increased from 1.4% in 1992 to 9.9% in 2002. The case fatality rate dropped from 81.9% to 33.9% in the period in question. An analysis of those who survived at least five years from the date of diagnosis showed that the percentage of patients treated increased from 46.2% in 1992 to 94.0% in 1997, finishing at 91.7% in 2002. Multivariate analysis yielded a positive and statistically significant association between survival up to five years after an AIDS diagnosis and years of schooling, age group, year of diagnosis, type of antiretroviral therapy, and treatment adherence (all with P < 0.001)., Conclusions: Continuous improvement of the antiretroviral therapy recommended by the Ministry of Health had a positive impact on survival. There was an association between case fatality and fewer years of schooling, membership in an older age group, a diagnosis obtained in 1992, the type of antiretroviral therapy, and suboptimal adherence to antiretroviral treatment regimens.

Introduction: Domestic dogs are the most important reservoir in the peridomestic transmission cycle of Leishmania (Leishmania) chagasi. The genetic variability of subpopulations of this parasite circulating in dogs has not been thoroughly analyzed in Brazil, even though this knowledge has important implications in the clinical-epidemiological context., Methods: The objective of this study was to evaluate and compare the phenotypic variability of 153 L. chagasi strains isolated from dogs originating from the municipalities of Rio de Janeiro (n = 57) and Belo Horizonte (n = 96), where the disease is endemic. Strains isolated only from intact skin were selected and analyzed by multilocus enzyme electrophoresis using nine enzyme systems (6PG, GPI, NH1 and NH2, G6P, PGM, MDH, ME, and IDHNADP)., Results: The electrophoretic profile was identical for all isolates analyzed and was the same as that of the L. chagasi reference strain (MHOM/BR/74/PP75). Phenetic analysis showed a similarity index of one for all strains, with the isolates sharing 100% of the characteristics analyzed., Conclusions: The results demonstrate that the L. chagasi populations circulating in dogs from Rio de Janeiro and Belo Horizonte belong to a single zymodeme.

Human immunodeficiency virus (HIV) clades B and C account for more than 60% of the HIV-1 infections worldwide. In this paper, we describe the profiles of patients infected with subtypes of HIV-1 from the state of Paraná, Southern Brazil, and correlate them with demographic and epidemiological findings. A retrospective analysis of HIV cases reported from 1999-2007 was also performed. Data from 293 patients were reviewed and 245 were older than 13 (58% female). The distribution of clades was as follows: B 140 (57%), C 67 (23%), F 24 (10%) and mosaic or unique recombinant forms (URFs) 24 (10%). Of the 48 patients younger than 13 years of age (62.5% male), vertical transmission occurred in 46 and the distribution of clades was as follows: B 14 (29%), C 24 (50%), F 7 (15%) and URFs 6 (13%). There was no significant difference in mortality between HIV-1 subtypes. In both groups, patients infected with clade C tended to have higher rates of injection drug use exposure risk.

In this article, we present the results of a study about mites associated with bats collected in the State of Pernambuco, northeast Brazil. Of the 331 bats collected, 23 were found naturally infested by mites, corresponding to an overall prevalence of 6.9% (95% confidence interval: 4.5-10.2). Four mite species were collected from seven bat species. The following mite-bat associations were recorded: Periglischrus acutisternus Machado-Allison on Phyllostomus discolor Wagner; Periglischrus ojastii Oudemans on Carollia perspicillata L.; Periglischrus iheringi Oudemans on Artibeus lituratus (Olfers), Artibeus planirostris Spix, Platyrrhinus lineatus (E. Geoffroy), and Sturnira lilium (E. Geoffroy); and Spelaeorhynchus praecursor Neumann on C. perspicillata. This study definitively confirms the presence of S. praecursor in Pernambuco and records for the first time the presence of three spinturnicid species (i.e., P. acutisternus, P. ojastii, and P. iheringi) in northeast Brazil.

Results from a cross-sectional observational study on candidemia conducted at Hospital de Clínicas, Federal University of Paraná, are presented. From January 2001 to December 2004, one hundred candidemia cases were evaluated. The incidence was 1.27 episodes per 1,000 hospitalizations and Candida was the eighth most frequently isolated agent from bloodstream infections. The patients ages ranged from five days to 89 years, with a mean of 32 years. Sixty percent of the cases occurred in adults (66% > 50 years old) and 40% in children (52% < one year old). Fifty-nine percent had been admitted to medical wards and 41% to the intensive care unit. Candida albicans was the most (59%) frequent species followed by Candida tropicalis (15%) and Candida parapsilosis (9%). The most (97%) prevalent coexisting conditions were the use of antibacterial drugs, central venous catheter (77%), H2 blockers (57%), total parenteral nutrition (49%) and admission to the intensive care unit (41%). Out of the 51 isolates tested, three of Candida glabrata presented dose-dependent susceptibility to fluconazole and resistance to itraconazole. One sample of Candida krusei presented dose-dependent susceptibility to fluconazole and one of Candida pelliculosa presented dose-dependent susceptibility to itraconazole. Among the study population, 68% received antifungal therapy, but the mortality was 56%.

Oncogenic human papillomaviruses (HPVs) are important agents in the genesis of gynecological cancer, and have also been implied in the genesis of oral cancer. With the purpose of evaluating the relationship between HPV and squamous cell carcinoma (SCC) of the tongue, a case-control study was performed. Fifty white male patients who were smokers and had the histological diagnosis of SCC of the tongue were selected. The control group was composed of 10 matched patients with no clinical evidence of tongue lesions. Polymerase chain reaction (PCR) was used to detect the presence of HPV genome in fresh-frozen tissue specimens from SCC of the tongue margin. Thirty-seven patients (74%) had a positive PCR for oncogenic papillomavirus, and only 1 specimen (10%) of the control group was positive for nononcogenic papillomavirus. Based on the statistical analysis of this study there was a 25.6% higher risk for SCC of the tongue to harbor oncogenic HPV than the healthy control tongue tissue.

Acute communitarian bacterial meningitis and AIDS are prevalent infectious disease in Brazil. The objective of this study was to evaluate the frequency of acute communitarian bacterial meningitis in AIDS patients, the clinical and cerebrospinal fluid (CSF) characteristics. It was reviewed the Health Department data from city of Curitiba, Southern Brazil, from 1996 to 2002. During this period, 32 patients with AIDS fulfilled criteria for acute bacterial meningitis, representing 0.84% of the AIDS cases and 1.85% of the cases of bacterial meningitis. S. pneumoniae was the most frequent bacteria isolated. The number of white blood cells and the percentage of neutrophils were higher and CSF glucose was lower in the group with no HIV co-infection (p 0.12; 0.008; 0.04 respectively). Bacteria not so common causing meningitis can occur among HIV infected patients. The high mortality rate among pneumococcus meningitis patients makes pneumococcus vaccination important.

Objective: To study prospectively the clinical features and laboratorial characteristics of 24 patients with central nervous system (CNS) involvement with paracoccidioidomycosis (PCM). PCM is an infectious disease caused by the dimorphic fungus Paracoccidioides brasiliensis, endemic in subtropical areas of Central and South America., Methods: From 173 cases of PCM, 24 (13.9%) had CNS involvement (NPCM) and were studied prospectively from 1993 to 1997. In all the patients, the diagnosis of systemic PCM was made by the demonstration of the P. brasiliensis organisms or positive serology, DID (double immunodiffusion). In seven cases the diagnosis was made by means of a CNS biopsy. CNS clinical manifestations, neuroimaging (CT or MRI) and CSF cytochemical characteristics were reported., Results: The mean age was 44 years (range 25-72 years); 23 patients were male, only one was female. Neurological symptoms began before systemic symptoms in 21%; simultaneously in 33%, and after systemic symptoms in 46%. Epilepsy was the more frequent neurological presentation (44%). Twenty-three cases had parenchymatous involvement and in two of these cases there was an association with meningitis and one case had spinal cord involvement. Lesions were more frequent in the brain hemispheres (69%), in 65% there were multiple granuloma characterized by hypodense images with annular or nodular enhancing. All cases were treated with sulphamethoxazole-trimethoprin. Four patients died, while 20 patients showed a good therapeutic response., Conclusion: NPCM should always be considered in the differential diagnosis of expanding lesions of the CNS and meningoencephalitis. Being alert to this diagnosis depends on knowledge of epidemiology. There was good response to sulphamethoxazole-trimethoprin treatment.

A retrospective study was performed to compare the prevalence of complications in peg-in-hole and end-to-end arthrodesis procedures. The authors reviewed 177 second, third, and fourth proximal interphalangeal joint fusions for the correction of hammer toe deformities in 85 patients from 1988 to 1998 at the Temple University School of Podiatric Medicine. The average age of the patients was 49 years. Sixteen percent (14) of the subjects were male and 84% were (71) female. Upon follow-up, the fourth digit was generally associated with a greater number of complications for the end-to-end and peg-in-hole procedures, with the second digit being the most common site of fusion. The prevalence of complications was evaluated using contingency table analysis and expressed as a percent of total complications (27%, the end-to-end group; 17%, the peg-in-hole group). A subset of complications deemed clinically relevant was also computed. Similarly, the prevalence of clinically relevant complications for the end-to-end (10%) and the peg-in-hole (9%) procedures was not statistically significant. Therefore, this study showed no statistically significant differences in the total or clinically relevant complications between end-to-end and the peg-in-hole arthrodesis procedures.

The proximal interphalangeal joint arthrodesis is frequently performed to correct hammer toe deformities. This study was conducted to compare the inherent stability of the three proximal interphalangeal joint arthrodeses--peg-in-hole, end-to-end, and V constructs--in the sagittal plane by means of load-to-failure testing of 30 fresh-frozen cadaveric specimens fixated with a 0.045 Kirschner wire. The peg-in-hole construct was associated with significantly higher peak loads at failure compared with the other two procedures. Furthermore, the peg-in-hole construct had significantly higher stiffness values as compared with the V procedure. This study thus provides evidence that the peg-in-hole procedure is the most biomechanically stable surgical construct for proximal interphalangeal joint fusions under sagittal plane loading.

We have previously reported that 5 alpha and 5 beta pathways of steroid metabolism are controlled in vivo by dietary Na+ and glycyrrhetinic acid, see Gorsline et al. 1988; Latif et al. 1990. The present investigations provide evidence supporting the suggestion that endogenous substances may regulate the glucocorticoid inactivating isoenzymes, 11 beta-HSD (hydroxysteroid dehydrogenase) 1 (liver) and 11 beta-HSD2 (kidney). The activity of 11 beta-HSD is impaired in essential hypertension, following licorice ingestion, and in patients with apparent mineralocorticoid excess where 11 beta-HSD2 is particularly affected. In all three conditions, excretion of the less common 5 alpha metabolites is elevated in urine. We now report on the differential abilities of a series of Ring A reduced (5 alpha and 5 beta) adrenocorticosteroid and progesterone metabolites to inhibit these isoenzymes. Using liver microsomes with NADP+ as co-factor (11 beta-HSD1), and sheep kidney microsomes with NAD+ as co-factor (11 beta-HSD2), we have systematically investigated the abilities of a number of adrenocorticosteroids and their derivatives to inhibit the individual isoforms of 11 beta-HSD. A striking feature is the differential sensitivity of the two isoenzymes to inhibition by 5 alpha and 5 beta derivatives. 11 beta-HSD1 is inhibited by both 5 alpha and certain 5 beta derivatives. 11 beta-HSD-2 was selectively inhibited only by 5 alpha derivatives: 5 beta derivatives were without inhibitory activity toward this isoform of 11 beta-HSD. These results indicate the importance of the structural conformation of the A and B Rings in conferring specific inhibitory properties on these compounds. In addition, we discuss the effects of additions or substitutions of other functional groups on the inhibitory potency of these steroid molecules against 11 beta-HSD1 and 11 beta-HSD2.

Lysozyme (LZM), immunoglobulin M (IgM) and C-reactive protein (CRP) levels were determined in cerebrospinal fluid (CSF) from patients classified on the basis of clinical and laboratory findings into three groups: bacterial meningitis (n = 33), lymphocytic meningitis (n = 21) and controls (n = 54). IgM and CRP levels were determined by enzyme-linked immunosorbent assay (ELISA) and LZM by the lysoplate method. Discriminant analysis demonstrated that 93.94% (31/33) and 96.97% (32/33) of patients with bacterial meningitis were correctly classified on the basis of CSF determinations of IgM and LZM, respectively. However, the measurement of CRP levels in CSF correctly classified 100% of these patients (33/33), thus representing a useful additional marker for the screening of bacterial meningitis. Moreover, no more than 4% (3/75) of patients were incorrectly classified as belonging to the bacterial group on the basis of the CRP test. Thus, CRP titres less than or equal to 80 identify cases belonging to one of the non-bacterial groups, whereas titres greater than or equal to 640 classify the bacterial group, with a very low chance of misclassification. The authors recommend that CSF IgM or LZM levels be also measured for patients with CSF CRP titres of 160 and 320, for a more accurate diagnosis. The probability of these cases being of bacterial aetiology, as calculated from the combined results of these measurements, is presented.