Association of calprotectin with other inflammatory parameters in the prediction of mortality for ischemic stroke.

BACKGROUND: Inflammatory response plays an important role in many processes related to acute ischemic stroke (AIS). Calprotectin (S100A8/S100A9), released by monocytes and neutrophils, is a key protein in the regulation of inflammation and thrombosis. The purpose of this study is to evaluate the association of circulating calprotectin with other inflammatory biomarkers and AIS prognosis, as well as the calprotectin content in stroke thrombi. METHODS: Among the 748 patients treated at a comprehensive stroke center between 2015 and 2017, 413 patients with confirmed acute ischemic injury were prospectively evaluated. Patients with systemic inflammation or infection at onset were excluded. Plasma calprotectin was measured by ELISA in blood samples of AIS patients within the first 24 h. Univariate and multivariate logistic regression models were performed to evaluate its association with mortality and functional independence (FI) at 3 months (defined as modified Rankin Scale < 3) and hemorrhagic transformation (HT) after ischemic stroke. Further, S100A9 was localized by immunostaining in stroke thrombi (n = 44). RESULTS: Higher calprotectin levels were associated with 3-month mortality, HT, and lower 3-month FI. After adjusting for potential confounders, plasma calprotectin remained associated with 3-month mortality [OR (95% CI) 2.31 (1.13-4.73)]. Patients with calprotectin ≥ 2.26 µg/mL were 4 times more likely to die [OR 4.34 (1.95-9.67)]. Addition of calprotectin to clinical variables led to significant improvement in the discrimination capacity of the model [0.91 (0.87-0.95) vs 0.89 (0.85-0.93); p < 0.05]. A multimarker approach demonstrated that patients with increased calprotectin, CRP, and NLR had the poorest outcome with a mortality rate of 42.3% during follow-up. S100A9 protein, as part of the heterodimer calprotectin, was present in all thrombi retrieved from AIS patients. Mean S100A9 content was 3.5% and tended to be higher in patients who died (p = 0.09). Moreover, it positively correlated with platelets (Pearson r 0.46, p < 0.002), leukocytes (0.45, p < 0.01), and neutrophil elastase (0.70, p < 0.001) thrombus content. CONCLUSIONS: Plasma calprotectin is an independent predictor of 3-month mortality and provides complementary prognostic information to identify patients with poor outcome after AIS. The presence of S100A9 in stroke thrombi suggests a possible inflammatory mechanism in clot formation, and further studies are needed to determine its influence in resistance to reperfusion.

Microencapsulated and Lyophilized Propolis Co-Product Extract as Antioxidant Synthetic Replacer on Traditional Brazilian Starch Biscuit.

The residue from commercial propolis extraction may have significant antioxidant power in food technology. However, among the challenges for using the propolis co-product as an inhibitor of lipid oxidation (LO) in baked goods is maintaining its bioactive compounds. Therefore, this study aimed to determine the propolis co-product extracts' capability to reduce LO in starch biscuit formulated with canola oil and stored for 45 days at 25 °C. Two co-product extracts were prepared: microencapsulated propolis co-product (MECP) (with maltodextrin) and lyophilized propolis co-product (LFCP), which were subjected to analysis of their total phenolic content and antioxidant activity (AA). Relevant antioxidant activity was observed using the methods of analysis employed. The spray-drying microencapsulation process showed an efficiency of 63%. The LO in the biscuits was determined by the thiobarbituric acid reactive substances (TBARS) test and fatty acid composition by gas chromatography analysis. Palmitic, stearic, oleic, linoelaidic, linoleic, and α-linolenic acids were found in biscuits at constant concentrations throughout the storage period. In addition, there was a reduction in malondialdehyde values with the addition of both propolis co-product extracts. Therefore, the propolis co-product extracts could be utilized as a natural antioxidant to reduce lipid oxidation in fatty starch biscuit.

Cerebrospinal fluid from Alzheimer patients affects cell-mediated nerve growth factor production and cell survival in vitro.

Alzheimer's disease (AD) is characterized by early degeneration of cholinergic neurons and decreased levels of nerve growth factor (NGF). Thus, increasing the NGF levels by for instance encapsulated cell bio-delivery (ECB) is a potential treatment strategy. The results from our previous first-in-human studies on ECB of NGF to the basal forebrain cholinergic neurons were promising, but indicated some variability of long-term viability of the encapsulated cells and associated reduced NGF-release. Here we studied the effect of amyloid beta-peptides (Aß), interleukin 1-beta (IL-1ß), and CSF from AD, Lewy body dementia (LBD) or subjective cognitive impairment (SCI) patients on the NGF overproducing cell line NGC-0295. At physiological concentrations, neither Aß40 nor Aß42 had any major impact on cell viability or NGF-production. In contrast, IL-1ß dose-dependently affected NGF-production over time. Exposure of NGF-producing cells to CSF from AD patients showed significantly reduced NGF-release as compared to CSF from LBD or SCI patients. By mass spectrometry we found 3 proteins involved in inflammatory pathways to have an altered expression in AD CSF compared to LBD and SCI. Cell survival and NGF-release were not affected by Aß. NGF-release was affected by IL-1ß, suggesting that inflammation has a negative effect on ECB cells.

Extraction and quantification of phenolic acids and flavonols from Eugenia pyriformis using different solvents.

The recovery of phenolic compounds of Eugenia pyriformis using different solvents was investigated in this study. The compounds were identified and quantified by reverse-phase high-performance liquid chromatography coupled with ultraviolet-visible diode-array detector (RP-HPLC-DAD/UV-vis). Absolute methanol was the most effective extraction agent of phenolic acids and flavonols (588.31 mg/Kg) from Eugenia pyriformis, although similar results (p ≤ 0.05) were observed using methanol/water (1:1 ratio). Our results clearly showed that higher contents of phenolic compounds were not obtained either with the most or the least polar solvents used. Several phenolic compounds were identified in the samples whereas gallic acid and quercetin were the major compounds recovered.

Role of factor XIII in ischemic stroke: a key molecule promoting thrombus stabilization and resistance to lysis.

BACKGROUND: Active coagulation factor XIII (FXIII) catalyzing crosslinking of fibrin and other hemostatic factors plays a key role in clot stability and lysis. OBJECTIVES: To evaluate the effect of FXIII inhibition in a mouse model of ischemic stroke (IS) and the role of activated FXIII (FXIIIa) in clot formation and lysis in patients with IS. METHODS: A ferric chloride IS murine model was performed before and after administration of a FXIIIa inhibitor (FXIIIinh). Thromboelastometry in human and mice blood was used to evaluate thrombus stiffness and lysis with FXIIIinh. FXIIIa-dependent fibrin crosslinking and lysis with fibrinolytic drugs (tissue plasminogen activator and tenecteplase) were studied on fibrin plates and on thrombi and clotted plasma of patients with IS. Finally, circulating and thrombus FXIIIa were measured in 85 patients with IS. RESULTS: FXIIIinh administration before stroke induction reduced infarct size, α2-antiplasmin (α2AP) crosslinking, and local microthrombosis, improving motor coordination and fibrinolysis without intracranial bleeds (24 hours). Interestingly, FXIII blockade after stroke also reduced brain damage and neurologic deficit. Thromboelastometry in human/mice blood with FXIIIinh showed delayed clot formation, reduced clot firmness, and shortened tissue plasminogen activator lysis time. FXIIIa fibrin crosslinking increased fibrin density and lysis resistance, which increased further after α2AP addition. FXIIIinh enhanced ex vivo lysis in stroke thrombi and fibrin plates. In patients with IS, thrombus FXIII and α2AP were associated with inflammatory and hemostatic components, and plasma FXIIIa correlated with thrombus α2AP and fibrin. CONCLUSION: Our results suggest a key role of FXIIIa in thrombus stabilization, α2AP crosslinking, and lysis resistance, with a protective effect of FXIIIinh in an IS experimental model.

The impact of immigration and vaccination in reducing the incidence of hepatitis B in Catalonia (Spain).

BACKGROUND: The Hepatitis B virus (HBV) infection is a major cause of liver disease and liver cancer worldwide according to the World Health Organization. Following acute HBV infection, 1-5% of infected healthy adults and up to 90% of infected infants become chronic carriers and have an increased risk of cirrhosis and primary hepatocellular carcinoma. The aim of this study was to investigate the relationship between the reduction in acute hepatitis B incidence and the universal vaccination programme in preadolescents in Catalonia (Spain), taking population changes into account, and to construct a model to forecast the future incidence of cases that permits the best preventive strategy to be adopted. METHODS: Reported acute hepatitis B incidence in Catalonia according to age, gender, vaccination coverage, percentage of immigrants and the year of report of cases was analysed. A statistical analysis was made using three models: generalized linear models (GLM) with Poisson or negative binomial distribution and a generalized additive model (GAM). RESULTS: The higher the vaccination coverage, the lower the reported incidence of hepatitis B (p <0.01). In groups with vaccination coverage > 70%, the reduction in incidence was 2-fold higher than in groups with a coverage <70% (p <0.01). The increase in incidence was significantly-higher in groups with a high percentage of immigrants and more than 15% (p <0.01) in immigrant males of working age (19-49 years). CONCLUSIONS: The results of the adjusted models in this study confirm that the global incidence of hepatitis B has declined in Catalonia after the introduction of the universal preadolescent vaccination programme, but the incidence increased in male immigrants of working age. Given the potential severity of hepatitis B for the health of individuals and for the community, universal vaccination programmes should continue and programmes in risk groups, especially immigrants, should be strengthened.

CM-352 Efficacy in a Mouse Model of Anticoagulant-Associated Intracranial Hemorrhage.

BACKGROUND: Intracranial hemorrhage (ICH) is one of the major devastating complications of anticoagulation. Matrix metalloproteinase (MMP) inhibition has been proposed as a novel pharmacological approach for ICH treatment. OBJECTIVES: We evaluated the effects of CM-352 (MMP-fibrinolysis inhibitor) in an experimental ICH model associated with oral anticoagulants as compared with clinically used prothrombin complex concentrate (PCC). METHODS: ICH was induced by collagenase injection into the striatum of wild type (C57BL/6J) anticoagulated mice (warfarin or rivaroxaban) and Mmp10 -/- mice. Hematoma volume and neurological deficits were measured 24 hours later by diaminobenzidine staining and different behavioral tests. Circulating plasminogen activator inhibitor-1 (PAI-1) activity and interleukin-6 (IL-6) were measured in plasma samples and local inflammation was assessed by neutrophil infiltration. Finally, fibrinolytic effects of MMP-10 and rivaroxaban were evaluated by thromboelastometry and thrombin-activatable fibrinolysis inhibitor (TAFI) activation assays. RESULTS: Only PCC reduced hemorrhage volume and improved functional outcome in warfarin-ICH, but both PCC and CM-352 treatments diminished hemorrhage volume (46%, p < 0.01 and 64%, p < 0.001, respectively) and ameliorated functional outcome in rivaroxaban-ICH. We further demonstrated that CM-352, but not PCC, decreased neutrophil infiltration in the hemorrhage area at 24 hours. The effect of CM-352 could be related to MMP-10 inhibition since Mmp10 -/- mice showed lower hemorrhage volume, better neurological score, reduced IL-6 levels and neutrophil infiltration, and increased PAI-1 after experimental ICH. Finally, we found that CM-352 reduced MMP-10 and rivaroxaban-related fibrinolytic effects in thromboelastometry and TAFI activation. CONCLUSION: CM-352 treatment, by diminishing MMPs and rivaroxaban-associated fibrinolytic effects, might be a novel antihemorrhagic strategy for rivaroxaban-associated ICH.

Tracking the immune response by MRI using biodegradable and ultrasensitive microprobes.

Molecular magnetic resonance imaging (MRI) holds great promise for diagnosis and therapeutic monitoring in a wide range of diseases. However, the low intrinsic sensitivity of MRI to detect exogenous contrast agents and the lack of biodegradable microprobes have prevented its clinical development. Here, we synthetized a contrast agent for molecular MRI based on a previously unknown mechanism of self-assembly of catechol-coated magnetite nanocrystals into microsized matrix-based particles. The resulting biodegradable microprobes (M3P for microsized matrix-based magnetic particles) carry up to 40,000 times higher amounts of superparamagnetic material than classically used nanoparticles while preserving favorable biocompatibility and excellent water dispersibility. After conjugation to monoclonal antibodies, targeted M3P display high sensitivity and specificity to detect inflammation in vivo in the brain, kidneys, and intestinal mucosa. The high payload of superparamagnetic material, excellent toxicity profile, short circulation half-life, and widespread reactivity of the M3P particles provides a promising platform for clinical translation of immuno-MRI.

Inside the Thrombus: Association of Hemostatic Parameters With Outcomes in Large Vessel Stroke Patients.

Background: Actual clinical management of ischemic stroke (IS) is based on restoring cerebral blood flow using tissue plasminogen activator (tPA) and/or endovascular treatment (EVT). Mechanical thrombectomy has permitted the analysis of thrombus structural and cellular classic components. Nevertheless, histological assessment of hemostatic parameters such as thrombin-activatable fibrinolysis inhibitor (TAFI) and matrix metalloproteinase 10 (MMP-10) remains unknown, although their presence could determine thrombus stability and its response to thrombolytic treatment, improving patient's outcome. Methods: We collected thrombi (n = 45) from large vessel occlusion (LVO) stroke patients (n = 53) and performed a histological analysis of different hemostatic parameters [TAFI, MMP-10, von Willebrand factor (VWF), and fibrin] and cellular components (erythrocytes, leukocytes, macrophages, lymphocytes, and platelets). Additionally, we evaluated the association of these parameters with plasma levels of MMP-10, TAFI and VWF activity and recorded clinical variables. Results: In this study, we report for the first time the presence of MMP-10 and TAFI in all thrombi collected from LVO patients. Both proteins were localized in regions of inflammatory cells, surrounded by erythrocyte and platelet-rich areas, and their content was significantly associated (r = 0.41, p < 0.01). Thrombus TAFI was lower in patients who died during the first 3 months after stroke onset [odds ratio (OR) (95%CI); 0.59 (0.36-0.98), p = 0.043]. Likewise, we observed that thrombus MMP-10 was inversely correlated with the amount of VWF (r = -0.30, p < 0.05). Besides, VWF was associated with the presence of leukocytes (r = 0.37, p < 0.05), platelets (r = 0.32, p < 0.05), and 3 months mortality [OR (95%CI); 4.5 (1.2-17.1), p = 0.029]. Finally, plasma levels of TAFI correlated with circulating and thrombus platelets, while plasma MMP-10 was associated with cardiovascular risk factors and functional dependence at 3 months. Conclusions: The present study suggests that the composition and distribution of thrombus hemostatic components might have clinical impact by influencing the response to pharmacological and mechanical therapies as well as guiding the development of new therapeutic strategies.

Influence of socioeconomic status on community-acquired pneumonia outcomes in elderly patients requiring hospitalization: a multicenter observational study.

BACKGROUND: The associations between socioeconomic status and community-acquired pneumonia outcomes in adults have been studied although studies did not always document a relationship.The aim of this multicenter observational study was to determine the association between socioeconomic status and community-acquired pneumonia outcomes in the elderly, in the context of a public health system providing universal free care to the whole population. METHODS: A total of 651 patients aged > or =65 years hospitalized due to community-acquired pneumonia through the emergency departments of five Spanish public hospitals were recruited and followed up between May 2005 and January 2007. The primary outcomes studied were: length of stay, intensive care unit admission, overall mortality and readmission. Socioeconomic status was measured using both individual and community data: occupation [categorized in six social groups (I, II, III, IVa, IVb and V)], educational level (< or = primary level or > or = secondary level) and disposable family income of the municipality or district of residence [>12,500 euro (high municipality family income) and < or =12,500 euro (low municipality family income)]. The six social groups were further categorized as upper/middle social class (groups I-IVb) and lower class (group V).Bivariate and multivariate analyses were performed. OR and their 95% confidence intervals were calculated. All statistical tests were two tailed and statistical significance was established as p < 0.05. RESULTS: 17.7% of patients lived in a municipality or district with a high municipality family income and 63.6% were upper/middle social class (I-IVb). Only 15.7% of patients had a secondary education. The adjusted analysis showed no association between pneumonia outcomes and social class, educational level or municipality family income. However, length of stay increased significantly in patients in whom the factors, living alone and being a smoker or ex-smoker coincided (p < 0.001). CONCLUSIONS: We measured socioeconomic status using both individual and community data and found no association between social class, educational level or municipality family income and the variables of pneumonia outcomes. The lack of differences between social classes supports the provision of universal, equitable health care by the public health system.

Circulating TIMP-1 is associated with hematoma volume in patients with spontaneous intracranial hemorrhage.

Matrix metalloproteinases (MMPs) are proteolytic zinc-endopeptidases regulated by tissue Inhibitors of matrix metalloproteinases (TIMPs). We evaluated the potential of MMPs and TIMPs as clinical tools for Intracranial Haemorrhage (ICH). Spontaneous non-traumatic ICH patients were recruited from two hospitals: Complejo Hospitalario de Navarra (CHN = 29) and Vall d´Hebron (VdH = 76). Plasmatic levels of MMP-1, -2, -7, -9, -10 and TIMP-1 and their relationship with clinical, radiological and functional variables were evaluated. We further studied the effect of TIMP-1 (0.05-0.2 mg/Kg) in an experimental tail-bleeding model. In CHN, TIMP-1 was associated with admission-hematoma volume and MMP-7 was elevated in patients with deep when compared to lobar hematoma. In VdH, admission-hematoma volume was associated with TIMP-1 and MMP-7. When data from both hospitals were combined, we observed that an increase in 1 ng/ml in TIMP-1 was associated with an increase of 0.14 ml in haemorrhage (combined ß = 0.14, 95% CI = 0.08-0.21). Likewise, mice receiving TIMP-1 (0.2 mg/Kg) showed a shorter bleeding time (p < 0.01). Therefore, the association of TIMP-1 with hematoma volume in two independent ICH cohorts suggests its potential as ICH biomarker. Moreover, increased TIMP-1 might not be sufficient to counterbalance MMPs upregulation indicating that TIMP-1 administration might be a beneficial strategy for ICH.

[Evaluation of mass vaccination programmes: the experience of Hepatitis A in Catalonia]. / Evaluación del impacto de los programas de vacunación masiva: la experiencia de la hepatitis A en Cataluña.

BACKGROUND: The hepatitis A + B vaccination programme of preadolescents was introduced in 1998 in Catalonia. During the following years, one of the main objectives has been to quantify the reduction in the incidence of hepatitis A caused by the vaccination programme. METHODS: A retrospective analysis applying the space-time scan statistic to reported incidence rates of hepatitis A was carried out in the counties of Catalonia from 1992 to 2007. The relative risk (RR) was calculated and the spatial autocorrelation was estimated using Moran's I statistic. RESULTS: Six of the 7 space-time clusters identified by the scan statistic occurred in the pre-vaccine era (1992-1998) and only one in the post-vaccine era (1992-2007). In the first 10 four-weekly periods of the post-vaccine era (1999-2005) there was a significant reduction in the incidence of hepatitis A in Catalonia with respect to the pre-vaccine era (1992-1998) (p<0,01). CONCLUSIONS: Moran's I statistic showed no pattern of global spatial dependence and was useful in detecting local clusters. These results corroborate previous studies that attributed most of the reduction in the incidence of hepatitis A in Catalonia to the effect of vaccination.

[Epidemiology of the meningococcal disease in Catalonia before and after vaccination against serogroup C]. / Epidemiología de la enfermedad meningocócica en Cataluña antes y después de la vacunación frente al serogrupo C.

BACKGROUNDS: Meningococcal disease remains a serious public health problem worldwide. In Catalonia, after implementing the vaccination program, there has been a significant decrease in cases caused by meningococcus C. METHODS: Reported cases of meningococcal disease between 1997 and 2008 were analyzed to determine the evolution after the introduction of a conjugated vaccine in Catalonia. RESULTS: In < 6 years, the incidence rate of serogroup C fell from 7.6 to 0.6 per 100,000 persons/year in the periods before (1997-2000) and after (2001-2007) the introduction of the conjugate vaccine. In serogroup B, the reduction was from 15.4 to 11.1. In < 20 years case-fatality-rate increased only in serogroup B (3% and 7.4%). Serosubtype P1.15was the most frequent in serogroup B (31%), mainly associated with serotype 4 (80%), and in serogroup C subtype P1.5 (36%), with serotype 2a (86%). During 2008, 5 apparently unrelated cases of B:2a:P1.5 were identified in the same geographic area, with a case-fatality-rate of 80%. CONCLUSIONS: Exhaustive surveillance of circulating meningococcal strains is essential.

MMP10 Promotes Efficient Thrombolysis After Ischemic Stroke in Mice with Induced Diabetes.

Diabetes is an important risk factor for ischemic stroke (IS). Tissue-type plasminogen activator (tPA) has been associated with less successful revascularization and poor functional outcome in diabetes. We assessed whether a new thrombolytic strategy based on MMP10 was more effective than tPA in a murine IS model of streptozotocin (STZ)-induced diabetes. Wild-type mice were administered a single dose of streptozotocin (STZ) (180 mg/kg) to develop STZ-induced diabetes mellitus. Two weeks later, IS was induced by thrombin injection into the middle cerebral artery and the effect of recombinant MMP10 (6.5 µg/kg), tPA (10 mg/kg) or tPA/MMP10 on brain damage and functional outcome were analysed. Motor activity was assessed using the open field test. Additionally, we studied plasminogen activator inhibitor-1 (PAI-1) and thrombin-antithrombin complex levels (TAT) by ELISA and oxidative stress and blood-brain barrier (BBB) integrity by immunohistochemistry and western blot. MMP10 treatment was more effective at reducing infarct size and neurodegeneration than tPA 24 h and 3 days after IS in diabetic mice. Locomotor activity was impaired by hyperglycemia and ischemic injury, but not by the thrombolytic treatments. Additionally, TAT, oxidative stress and BBB permeability were reduced by MMP10 treatment, whereas brain bleeding or PAI-1 expression did not differ between treatments. Thrombolytic treatment with MMP10 was more effective than tPA at reducing stroke and neurodegeneration in a diabetic murine model of IS, without increasing haemorrhage. Thus, we propose MMP10 as a potential candidate for the clinical treatment of IS in diabetic patients.

Estimated incidence of hepatitis A virus infection in Catalonia.

PURPOSE: Hepatitis A normally is underreported by statutory disease reporting systems. The objective of this study is to estimate the incidence of hepatitis A virus (HAV) infection from prevalence surveys of infection carried out in representative samples of the population in 1989, 1996, and 2002 and the reported disease incidence during 1991 to 2003 in Catalonia. METHODS: The real incidence of the infection was estimated from the reported incidence adjusted by the prevalence of susceptible individuals and the probability of presenting clinical manifestations. The bootstrap resampling technique was used to calculate 95% confidence intervals (CIs) of reported, clinical, and all infection cases. RESULTS: The infection rate estimated by the bootstrap method was 31.1/100,000 person-years (bootstrap studentized 95% CI, 19.4-56.0), and the rate of clinical hepatitis was 20.0/100,000 person-years (95% CI, 11.8-39.9), rates that were 6.3 and 4.1 times greater than the reported rate during the same period, respectively. CONCLUSIONS: In children younger than 5 years, the estimated infection rate was 13.8 times greater than the reported rate. Combined use of reported cases and results of seroprevalence surveys suggest that underreporting of HAV infection is substantial in Catalonia, especially in children younger than 5 years.

Estimate of influenza cases using generalized linear, additive and mixed models.

We investigated the relationship between reported cases of influenza in Catalonia (Spain). Covariates analyzed were: population, age, data of report of influenza, and health region during 2010-2014 using data obtained from the SISAP program (Institut Catala de la Salut - Generalitat of Catalonia). Reported cases were related with the study of covariates using a descriptive analysis. Generalized Linear Models, Generalized Additive Models and Generalized Additive Mixed Models were used to estimate the evolution of the transmission of influenza. Additive models can estimate non-linear effects of the covariates by smooth functions; and mixed models can estimate data dependence and variability in factor variables using correlations structures and random effects, respectively. The incidence rate of influenza was calculated as the incidence per 100 000 people. The mean rate was 13.75 (range 0-27.5) in the winter months (December, January, February) and 3.38 (range 0-12.57) in the remaining months. Statistical analysis showed that Generalized Additive Mixed Models were better adapted to the temporal evolution of influenza (serial correlation 0.59) than classical linear models.

[Meningococcal disease in Catalonia, Spain (1990-1997)]. / Enfermedad meningocócica en Cataluña (1990-1997).

BACKGROUND AND OBJECTIVE: We aimed to study the behavior of meningococcal disease in Catalonia during the period 1990-1997, identifying the possible epidemic periods. MATERIAL AND METHOD: All cases reported to the notifiable disease system which fulfilled the criteria of confirmed or suspected cases during this period were analyzed. RESULTS: The global incidence rate was 4.8/100,000. The incidence rate for serogroup B was 1.9/100,000 and for serogroup C 0.8/100,000. The disease incidence tended to diminish slightly during the study period, with a constant annual growth of 0.11/100,000. The increased incidence of serogroup C cases in 1996-1997 was associated with an increased incidence in the 10-19 years age group. CONCLUSIONS: Globally, in the 1990-1997 period, the disease incidence tended to diminish slightly. During the last two years, an increased incidence was observed, mostly due to the increase in the number of serogroup C cases. This fact was associated with a change in the age pattern of cases, which increased in the 10-19 years age group, as observed in other countries and coinciding with epidemic periods or greater meningococcal activity.

Changes in the evolution of meningococcal disease, 2001-2008, Catalonia (Spain).

Reported cases of meningococcal disease between 1997 and 2008 were analyzed to determine the evolution after the introduction of a conjugated vaccine. In <6 years, the incidence rate of serogroup C fell from 7.6 to 0.6 per 100,000 persons/year in the periods before (1997-2000) and after (2001-2007) the introduction of the conjugate vaccine. In serogroup B, the reduction was from 15.4 to 11.1. In <20 years case-fatality-rate increased only in serogroup B (3% and 7.4%, p=0.026). Serosubtype P1.15 was the most frequent in serogroup B (31%), mainly associated with serotype 4 (80%), and in serogroup C subtype P1.5 (36%), with serosubtype 2a (86%). Exhaustive surveillance of circulating meningococcal strains is essential.

Is the vaccination coverage established enough to control pertussis, or it is a re-emerging disease?

Although vaccination coverage is high in Catalonia, Spain, pertussis is still a significant cause of morbidity and mortality among infants, overall due to adolescent and adult contacts. An epidemiological study from voluntary health care centres to detect confirmed pertussis cases was carried out in Catalonia. From 465 pertussis-suspect-cases, we identified 126 confirmed events, 73 of them confirmed by laboratory tests. Most of cases were infants less than 4 months old 23 (18.3%), adolescents 22 (17.4%) and adults 46 (36.5%). Sixty-one cases (49.6%) presented paroxysmal cough, 33 (26.8%) post-tussive vomiting and inspiratory whoop, and 27 (22%) apnoea. The vaccination status was not known for 46 (36.5%) patients. Of the total vaccine status documented, 59 (73.8%) patients had received at least one dose. Sixty patients (47.6%) were considered index cases, 32 of them (53.3%) were children under 1-year old. Among contacts identified as pertussis cases, 63.6% (42/66) were older than 14 years of age. These contacts were parents (30), siblings (19), grandmother (4), and others (13). These results confirm protective efficacy of pertussis vaccine only during few time. Regular pertussis boosters in teenagers, and/or in adults who take care of young children, could decrease the incidence of the infection.

Mumps: a year of enhanced surveillance in Catalonia, Spain.

Mumps is a vaccine-preventable disease candidate for elimination. Positive predictive value (PPV) of clinical case definition was assessed. During 2007, 410 suspected cases were reported in Catalonia: 348 fulfilled clinical case definition and 159 were laboratory confirmed. Incidence rate was 4.8 per 100,000 for cases that fulfilled the clinical definition, and 2.2 for laboratory confirmed cases. Global PPV was 44.5%; 38.5% in <15 years and 50% in > or =15 years (p=0.04). Most laboratory confirmed cases (72.3%) received at least one MMR dose. With sustained high MMR coverage, laboratory confirmation is necessary to control the disease and assess vaccine failure.