Three-year multicenter surveillance of community-acquired Listeria monocytogenes meningitis in adults

BACKGROUND. Listeria monocytogenes is the third most frequent cause of bacterial meningitis. The aim of this study is to know the incidence and risk factors associated with development of acute community-acquired Lm meningitis in adult patients and to evaluate the clinical features, management, and outcome in this prospective case series. METHODS. A descriptive, prospective, and multicentric study carried out in 9 hospitals in the Spanish Network for Research in Infectious Diseases (REIPI) over a 39-month period. All adults patients admitted to the participating hospitals with the diagnosis of acute community-acquired bacterial meningitis (Ac-ABM) were included in this study. All these cases were diagnosed on the basis of a compatible clinical picture and a positive cerebrospinal fluid (CSF) culture or blood culture. The patients were followed up until death or discharge from hospital. RESULTS. Two hundred and seventy-eight patients with Ac-ABM were included. Forty-six episodes of Lm meningitis were identified in 46 adult patients. In the multivariate analysis only age (OR 1.026; 95% CI 1.00-1.05; p = 0.042), immunosuppression (OR 2.520; 95% CI 1.05-6.00; p = 0.037), and CSF/blood glucose ratio (OR 39.42; 95% CI 4.01-387.50; p = 0.002) were independently associated with a Lm meningitis. The classic triad of fever, neck stiffness and altered mental status was present in 21 (49%) patients, 32% had focal neurological findings at presentation, 12% presented cerebellum dysfunction, and 9% had seizures. Twenty-nine (68%) patients were immunocompromised. Empirical antimicrobial therapy was intravenous ampicillin for 34 (79%) of 43 patients, in 11 (32%) of them associated to aminoglycosides. Definitive ampicillin plus gentamicin therapy was significantly associated with unfavourable outcome (67% vs 28%; p = 0.024) and a higher mortality (67% vs 32%; p = 0.040).The mortality rate was 28% (12 of 43 patients) and 5 of 31 (16.1%) surviving patients developed adverse clinical outcome. CONCLUSIONS Elderly or immunocompromised patients, and a higher CSF/blood glucose ratio in patients with Ac-ABM must alert clinicians about Lm aetiology. Furthermore, we observed a high incidence of acute community-acquired Lm meningitis in adults and the addition of aminoglycosides to treatment should be avoid in order to improve the patients' outcome. Nevertheless, despite developments in intensive care and antimicrobial therapy, this entity is still a serious disease that carries high morbidity and mortality rates.

Anti-Toxoplasma gondii secretory IgA in tears of patients with ocular toxoplasmosis: immunodiagnostic validation by ELISA

Toxoplasma gondii causes posterior uveitis and the specific diagnosis is based on clinical criteria. The presence of anti-T. gondii secretory IgA (sIgA) antibodies in patients' tears has been reported and an association was found between ocular toxoplasmosis and the anti-T. gondii sIgA isotype in Brazilian patients. The purpose of this study was to provide an objective validation of the published ELISA test for determining the presence of anti-T. gondii sIgA in the tears of individuals with ocular toxoplasmosis. Tears from 156 patients with active posterior uveitis were analysed; 82 of them presented characteristics of ocular toxoplasmosis (standard lesion) and 74 patients presented uveitis due to other aetiologies. Cases of active posterior uveitis were considered standard when a new inflammatory focus satellite to old retinochoroidal scars was observed. The determination of anti-T. gondii sIgA was made using an ELISA test with crude tachyzoite antigenic extracts. Tears were collected without previous stimulation. Detection of sIgA showed 65.9% sensitivity (95% CI = 54.5-74.4), 71.6% specificity (95% CI = 59.8-81.2), a positive predictive value of 72% (95% CI = 60.3-81.5) and a negative predictive value of 65.4% (95% CI = 54.0-75.4). sIgA reactivity was higher in the tears of patients with active posterior uveitis due to T. gondii (p < 0.05). The test is useful for differentiating active posterior uveitis due to toxoplasmosis from uveitis caused by other diseases.

Candidate gene analysis of ocular toxoplasmosis in Brazil: evidence for a role for toll-like receptor 9 (TLR9)

Toxoplasma gondii infection is an important mediator of ocular disease in Brazil more frequently than reported from elsewhere. Infection and pathology are characterized by a strong proinflammatory response which in mice is triggered by interaction of the parasite with the toll-like receptor (TLR)/MyD88 pathway. A powerful way to identify the role of TLRs in humans is to determine whether polymorphisms at these loci influence susceptibility to T. gondii-mediated pathologies. Here we report on a small family-based study (60 families; 68 affected offspring) undertaken in Brazil which was powered for large effect sizes using single nucleotide polymorphisms with minor alleles frequencies > 0.3. Of markers in TLR2, TLR5 and TLR9 that met these criteria, we found an association Family Based Association Tests [(FBAT) Z score = 4.232; p = 1.5 x 10-5; p corrected = 1.2 x 10-4] between the C allele (frequency = 0.424; odds ratio = 7; 95% confidence interval 1.6-30.8) of rs352140 at TLR9 and toxoplasmic retinochoroiditis in Brazil. This supports the hypothesis that direct interaction between T. gondii and TLR9 may trigger proinflammatory responses that lead to severe pathologies such as the ocular disease that is associated with this infection in Brazil.

MAGE-A3 and MAGE-A4 specific CD4(+) T cells in head and neck cancer patients: detection of naturally acquired responses and identification of new epitopes.

Frequent expression of cancer testis antigens (CTA) has been consistently observed in head and neck squamous cell carcinomas (HNSCC). For instance, in 52 HNSCC patients, MAGE-A3 and -A4 CTA were expressed in over 75% of tumors, regardless of the sites of primary tumors such as oral cavity or hypopharynx. Yet, T-cell responses against these CTA in tumor-bearing patients have not been investigated in detail. In this study, we assessed the naturally acquired T-cell response against MAGE-A3 and -A4 in nonvaccinated HNSCC patients. Autologous antigen-presenting cells pulsed with overlapping peptide pools were used to detect and isolate MAGE-A3 and MAGE-A4 specific CD4(+) T cells from healthy donors and seven head and neck cancer patients. CD4(+) T-cell clones were characterized by cytokine secretion. We could detect and isolate MAGE-A3 and MAGE-A4 specific CD4(+) T cells from 7/7 cancer patients analyzed. Moreover, we identified six previously described and three new epitopes for MAGE-A3. Among them, the MAGE-A3(111-125) and MAGE-A3(161-175) epitopes were shown to be naturally processed and presented by DC in association with HLA-DP and DR, respectively. All of the detected MAGE-A4 responses were specific for new helper epitopes. These data suggest that naturally acquired CD4(+) T-cell responses against CT antigens often occur in vivo in HNSCC cancer patients and provide a rationale for the development of active immunotherapeutic approaches in this type of tumor.

IgG and IgM western blot assay for diagnosis of congenital toxoplasmosis

The aim of this study was to evaluate the utility of western blot (WB) analysis as a diagnostic tool for congenital toxoplasmosis in 215 newborn infants. The children were submitted to clinical examinations to assess macular, neurological and hearing signals. The WB results obtained were compared to the persistence of IgG antibodies at the end of 12 months, which is regarded as the "gold standard" diagnosis of congenital toxoplasmosis. Association between the WB results and the clinical signs presented by the infants was also assessed. Of the 215 children, 177 had a confirmed congenital toxoplasmosis diagnosis and 38 were uninfected. IgG-WB showed a sensitivity of 73.5% and a specificity of 97.4%. IgM-WB showed a sensitivity of 54.8% and a specificity of 94.7%. The IgG-WB and IgM-WB combination increased the sensitivity to 86.5%. The IgM-WB-positive children had a 1.4-fold greater risk of presenting active macular lesions than did those that were IgM-WB-negative. This study showed that the WB assay is a useful tool to confirm a diagnosis of congenital toxoplasmosis and that the IgM-WB-positive results can indicate active macular lesions in newborn infants.

Ocular toxoplasmosis: evaluation of lacrimal - specific secretory IgA levels in both patients with active and inactive phases of the disease

Ocular toxoplasmosis can result in recurrent uveitis. Studies have shown that a correlation between active ocular toxoplasmosis and the presence of anti-Toxoplasma gondii secretory IgA (SIgA) in tears. This study compares anti-T. gondii SIgA levels in patients' tears during the acute and inactive phases of toxoplasmic uveitis. Twenty-nine positive tear specific SIgA for T. gondii patients with acute toxoplasmic uveitis were selected and were followed-up for at least two years, when the anti-T. gondii SIgA tears levels were determined. Specific SIgA for T. gondii was negative in 22 patients (75.86%) and positive in seven patients (24.13%) of whom six (85.7%) were followed over three years. Average SIgA levels during the acute phase are 1.54 and decrease significantly to 0.72 (p = 0.0001) during the inactive phase of disease. Because anti-T. gondii SIgA in the tear is negative in 75.86% of patients after the acute phase of infection, T. gondii SIgA levels may be used as a complementary diagnostic marker for active ocular toxoplasmosis.

Fièvre, adénopathie: une situation clinique de toxoplasmose aiguë chez une patiente immunocompétente [Fever and lymphadenopathy: acute toxoplasmosis in an immunocompetent patient].

Toxoplasmosis is an infectious disease caused by the intracellular parasite Toxoplasma gondii. In Switzerland about a third of the population has antibodies against this pathogen and has thus already been in contact with the parasite or has contracted the disease. Immunocompetent patients are usually asymptomatic (80-90%) during primary infection. The most common symptom is neck or occipital lymphadenopathy. Serology is the diagnostic gold standard in immunocompetent individuals. The presence of IgM antibodies is however not sufficient to make a definite diagnosis of acute toxoplasmosis. Distinction between acute and chronic toxoplasmosis requires additional serological tests (IgG avidity test). If required, the most used and probably most effective treatment is the combination of pyrimethamine and sulfadiazine, with folinic acid.

Depletion of CD25+ cells during acute toxoplasmosis does not significantly increase mortality in Swiss OF1 mice

The interleukin (IL)-2R alpha chain (CD25) is expressed on regulatory T cells (Treg), which constitute more than 85% of the CD25+ T cell population in a naïve mouse. CD25 is also expressed on effector T cells in mice suffering from an acute infection by the obligate intracellular protozoan parasite, Toxoplasma gondii. Lethal toxoplasmosis is accompanied by a significant loss of Treg in mice naturally susceptible to toxoplasmosis. The present study was done to explore the role of Treg cells using an anti-CD25 antibody-mediated depletion in mice naturally resistant to toxoplasmosis. Although a significant decrease in the percentage of Treg cells was observed following anti-CD25 monoclonal antibody injections, the depletion of CD25+ cells during acute toxoplasmosis did not significantly increase the mortality of Swiss OF1 mice and no significant difference was observed in the brain parasitic load between the mice in the depleted-infected and isotype-infected groups. We found no significant difference between the titres of total IgG in the sera of the mice from the two groups in the chronic phase. However, CD25+ cells depletion was followed by significantly higher levels of IL-12 in the serum of depleted mice than in that of mice injected with the isotype control antibody.

Early diagnosis of congenital toxoplasmosis in newborn infants using IgG subclasses against two Toxoplasma gondii recombinant proteins

The aim of this work was to evaluate the utility of ELISA-based testing of total IgG (IgGt) antibodies and its subclasses (IgG1, IgG2, IgG3 and IgG4) against soluble (STAg) and recombinant (rSAG1 and rMIC3) antigens of Toxoplasma gondii for diagnosing congenital toxoplasmosis. Sera from 217 newborns initially testing positive for specific IgM in filter paper dried blood spots were tested for specific IgM and IgG by ELFA-VIDAS®. Congenital toxoplasmosis was confirmed in 175 and ruled out in 42 infants. The validity of the ELISA tests was determined using the persistence of IgG antibodies (ELFA-VIDAS® kit) at the end of 12 months, which is considered the reference test for the diagnosis of congenital toxoplasmosis. The frequency of positivity with IgGt against STAg, rSAG1 and rMIC3 was found in 97.2%, 96.3% and 80.2%, respectively, of the newborns with confirmed congenital toxoplasmosis. IgG1 reacted with all three antigens, while IgG3 and IgG4 reacted preferentially with rMIC3. Higher mean values of reactivity (sample optical density/cut-off) were found for all subclasses when using rMIC3. All of the antigens showed high sensitivity and low specificity in detecting anti-T. gondii IgGt and IgG1 and low sensitivity and high specificity in detecting IgG3 and IgG4. In conclusion, the combined detection of IgG antibody subclasses against recombinant toxoplasmic antigens may be useful for the early diagnosis of congenital toxoplasmosis.

International recommendations on the diagnosis and treatment of patients with acquired hemophilia A.

Acquired hemophilia A (AHA) is a rare bleeding disorder characterized by autoantibodies directed against circulating coagulation factor (F) VIII. Typically, patients with no prior history of a bleeding disorder present with spontaneous bleeding and an isolated prolonged aPTT. AHA may, however, present without any bleeding symptoms, therefore an isolated prolonged aPTT should always be investigated further irrespective of the clinical findings. Control of acute bleeding is the first priority, and we recommend first-line therapy with bypassing agents such as recombinant activated FVII or activated prothrombin complex concentrate. Once the diagnosis has been achieved, immediate autoantibody eradication to reduce subsequent bleeding risk should be performed. We recommend initial treatment with corticosteroids or combination therapy with corticosteroids and cyclophosphamide and suggest second-line therapy with rituximab if first-line therapy fails or is contraindicated. In contrast to congenital hemophilia, no comparative studies exist to support treatment recommendations for patients with AHA, therefore treatment guidance must rely on the expertise and clinical experience of specialists in the field. The aim of this document is to provide a set of international practice guidelines based on our collective clinical experience in treating patients with AHA and contribute to improved care for this patient group.

Time-based distribution of Staphylococcus saprophyticus pulsed field gel-electrophoresis clusters in community-acquired urinary tract infections

The epidemiology of urinary tract infections (UTI) by Staphylococcus saprophyticus has not been fully characterised and strain typing methods have not been validated for this agent. To evaluate whether epidemiological relationships exist between clusters of pulsed field gel-electrophoresis (PFGE) genotypes of S. saprophyticus from community-acquired UTI, a cross-sectional surveillance study was conducted in the city of Rio de Janeiro, Brazil. In total, 32 (16%) female patients attending two walk-in clinics were culture-positive for S. saprophyticus. Five PFGE clusters were defined and evaluated against epidemiological data. The PFGE clusters were grouped in time, suggesting the existence of community point sources of S. saprophyticus. From these point sources, S. saprophyticus strains may spread among individuals.

Toxoplasmosis seroprevalence in urban rodents: a survey in Niamey, Niger

A serological survey of Toxoplasma gondii was conducted on 766 domestic and peridomestic rodents from 46 trapping sites throughout the city of Niamey, Niger. A low seroprevalence was found over the whole town with only 1.96% of the rodents found seropositive. However, differences between species were important, ranging from less than 2% in truly commensal Mastomys natalensis, Rattus rattus and Mus musculus, while garden-associated Arvicanthis niloticus displayed 9.1% of seropositive individuals. This is in line with previous studies on tropical rodents - that we reviewed here - which altogether show that Toxoplasma seroprevalence in rodent is highly variable, depending on many factors such as locality and/or species. Moreover, although we were not able to decipher statistically between habitat or species effect, such a contrast between Nile grass rats and the other rodent species points towards a potentially important role of environmental toxoplasmic infection. This would deserve to be further scrutinised since intra-city irrigated cultures are extending in Niamey, thus potentially increasing Toxoplasma circulation in this yet semi-arid region. As far as we are aware of, our study is one of the rare surveys of its kind performed in Sub-Saharan Africa and the first one ever conducted in the Sahel.

Effectiveness of holistic neuropsychological rehabilitation for Spanish population with acquired brain injury measured using Rasch analysis.

INTRODUCTION The Rasch model is increasingly used in the field of rehabilitation because it improves the accuracy of measurements of patient status and their changes after therapy. OBJECTIVE To determine the long-term effectiveness of a holistic neuropsychological rehabilitation program for Spanish outpatients with acquired brain injury (ABI) using Rasch analysis. METHODS Eighteen patients (ten with long evolution - patients who started the program > 6 months after ABI- and eight with short evolution) and their relatives attended the program for 6 months. Patients' and relatives' answers to the European Brain Injury Questionnaire and the Frontal Systems Behavior Scale at 3 time points (pre-intervention. post-intervention and 12 month follow-up) were transformed into linear measures called logits. RESULTS The linear measures revealed significant improvements with large effects at the follow-up assessment on cognitive and executive functioning, social and emotional self-regulation, apathy and mood. At follow-up, the short evolution group achieved greater improvements in mood and cognitive functioning than the long evolution patients. CONCLUSIONS The program showed long-term effectiveness for most of the variables, and it was more effective for mood and cognitive functioning when patients were treated early. Relatives played a key role in the effectiveness of the rehabilitation program.