Risk factors for death from invasive pneumococcal disease, europe, 2010

We studied the possible association between patient age and sex, clinical presentation, Streptococcus pneumoniae serotype, antimicrobial resistance, and death in invasive pneumococcal disease cases reported by 17 European countries during 2010. The study sample comprised 2,921 patients, of whom 56.8% were men and 38.2% were >65 years of age. Meningitis occurred in 18.5% of cases. Death was reported in 264 (9.0%) cases. Older age, meningitis, and nonsusceptibility to penicillin were signifcantly asso ciated with death. Non-pneumococcal conjugate vaccine (PCV) serotypes among children 65 years of age, risk did not differ by serotype. These fndings highlight differences in case-fatality rates between sero types and age; thus, continued epidemiologic surveillance across all ages is crucial to monitor the long-term effects of PCVs

Erythromycin-Resistant Group A Streptococcal Isolates Recovered in Sofia, Bulgaria, from 1995 to 2001

The frequency of erythromycin resistance within group A streptococci in Sofia, Bulgaria, from 1995 to 2001 was 2.1% (26 isolates). Of this, 57.7% was macrolide-lincosamide-streptogramin (MLS) inducible, 7.7% was MLS constitutive, and 34.6% had the M phenotype. Eleven different emm sequence types were found among 25 erythromycin-resistant isolates tested. Nineteen of 26 erythromycin-resistant isolates were additionally resistant to tetracycline and/or chloramphenicol

Cyclosporine induces glomerulosclerosis: Three-dimensional definition of the lesions in a rat model of renal transplant

Cyclosporine induces glomerulosclerosis: Three-dimensional definition of the lesions in a rat model of renal transplant. Previous description of chronic cyclosporine (CsA) renal toxicity commonly included vascular changes, tubular atrophy, and interstitial fibrosis. Glomerular injury was only occasionally documented and it is not clear whether glomerular changes may have an impact on the clinical syndrome of CsA toxicity observed in experimental animals and humans. At the moment the prevailing view is that when patients given CsA have glomerular lesions at a renal biopsy, these were due to concomitant chronic rejection or renal hypoperfusion rather than to CsA itself. As a follow-up of our previous work on the subject (abstract; J Am Soc Nephrol 2:1398, 1992) the present study was undertaken to clarify whether CsA is a direct cause of glomerular injury. We used a model of renal transplant among Lewis rats to better mimic the condition in which CsA is given to humans. Animals underwent kidney isografts and were given daily CsA or vehicle for as long as 12 months. At the end of the experiment specimens of renal tissue were analyzed by a serial section morphometric analysis technique, which allows precise evaluation at the individual glomerular level, glomerular volume and percentage of the capillary tuft affected by sclerosis. Among 85 glomeruli from CsA-treated rats, examined by three-dimensional morphometric analysis, only 12% were normal and 88% revealed segmental sclerosis. Data of single-section analysis compared with three-dimensional morphometric reconstruction showed that the former markedly underestimated the extent of glomerular injury. By three-dimensional analysis we showed that chronic CsA administration was associated with profound changes in glomerular capillary tuft volume distribution as compared to normal. Specifically, a subset of smaller than normal glomeruli emerged in CsA-treated animals in addition to a population of glomeruli which were larger than normal. No significant correlation was found between capillary tuft volume and sclerosis volume. These findings indicate that chronic administration of CsA induces in rats glomerular lesions comparable to the ones reported in human renal or heart transplant. Our present model may help investigating the mechanism(s) of chronic CsA renal toxicity, and will provide important clues for pharmacological manipulations aimed at reducing the long-term consequences of CsA on the kidney

NEONATAL INVASIVE GROUP B STREPTOCOCCAL (GBS) INFECTIONS IN EUROPE

Objectives: To describe clinical characteristics and capsular type of GBS isolates responsible of invasive infections in infants from Belgium, Bulgaria, Czech-Republic, Denmark, Germany, Italy, Spain and United Kingdom, representing one of the main objectives of the DEVANI (DEsign of a Vaccine Against Neonatal Infections) project. Methods: Surveillance of invasive GBS infections in infants was performed from mid-2008 through December 2010. For each case, a standardized case report form was filled. Samples from cases were processed using local procedures. GBS isolates were characterised in national central labs using standardised type-specific (Ia, Ib-IX) latex agglutination and molecular typing methods. Results: Data on 188 infants with invasive infection were analysed: 144 (60.6%) early onset diseases (EOD) and 74 (39.4%) late onset diseases (LOD). In EOD, mean/median ages at onset were 14/0 hours and the male:female ratio was 1.25. The predominant manifestation at onset was respiratory distress (42% cases); 83% cases were associated with sepsis/bacteremia, 15% with pneumonia and 6% with meningitis. Late-prenatal screening cultures were obtained from 51% of cases’ mothers and only half of these were positive for GBS. Non-elective C-section, intrapartum fever and rupture of membrane (>18h) were more frequent in EO-cases’ mothers versus healthy babies’ GBS-positive mothers. The major serotypes were III (43%), V (21%) and Ia (18%). In LOD, mean/median ages at onset were 42/34 days and the male:female ratio was 0.9. The predominant characteristic at onset was fever (62% cases); 70% cases were associated with sepsis and 30% with meningitis. Very rare manifestations were osteomyelitis and cellulitis. Serotype III was highly predominant (80.6%) followed mainly by Ia (12.5%). Death rates were 4.7/1.5% in EOD/LOD. Conclusions: Clinical presentations were associated with age at onset of infection. Serotype III predominated in neonatal infections. Prenatal screening was not universal neither sensitive. Study funded through the European Commission Seventh Framework.DEVANI (DEsign of a Vaccine Against Neonatal Infections) Project full title: Design of a vaccine to immunize neonates against GBS infections through a durable maternal immune response

Pili genes pattern in Group B streptococci from newborn infections and pregnant women in Europe (DEVANI Project)

Objectives Evaluation of the presence and expression of genes coding for pili in a collection of group B streptococcci (GBS) isolated from newborn infection and pregnant women in the course of the DEVANI (Design of a Vaccine Against Neonatal Infection) project. Methods GBS isolates from pregnant women (PW) and cases of newborn infection (NI) were collected in 8 European countries (Belgium, Bulgaria, Czech Republic, Denmark, Germany, Italy, Spain, United Kingdom) during 2009/10 under the auspices of DEVANI. Total no. of strains examined was 1078 and 192 from PW and NI, respectively. Isolates were screened by multiplex PCR and FACS analysis to evaluate respectively gene presence and surface-exposure of pili. Results The most common gene patterns found were PI-2a alone, PI 1+2a and PI 1+2b, while the PI-2b gene alone was very rare. The most prominent result was that a majority of isolates from NI carried the PI-1+2b gene pattern, while the most common pattern among PW was PI-1+2a. Most of analyzed strains express at least one pilus on their surface. Conclusions All isolates contained at least one gene coding for pili. When present pili 2a and 2b were highly surface exposed

External Quality Assessment for the Determination of Diphtheria Antitoxin in Human Serum▿

Accurate determination of diphtheria toxin antibodies is of value in determining the rates of immunity within broad populations or the immune status of individuals who may be at risk of infection, by assessing responses to vaccination and immunization schedule efficacy. Here we report the results of an external quality assessment (EQA) study for diphtheria serology, performed within the dedicated surveillance network DIPNET. Twelve national laboratories from 11 European countries participated by testing a standard panel of 150 sera using their current routine method: Vero cell neutralization test (NT), double-antigen enzyme-linked immunosorbent assay (ELISA; DAE), dual double-antigen time-resolved fluorescence immunoassay (dDA-DELFIA), passive hemagglutination assay (PHA), toxin binding inhibition assay (ToBI), and in-house or commercial ELISAs. The objective of the study was not to identify the best assay, as the advantages and drawbacks of methods used were known, but to verify if laboratories using their routine method would have categorized (as negative, equivocal, or positive) a serum sample in the same way. The performance of each laboratory was determined by comparing its results on a quantitative and qualitative basis to NT results from a single reference laboratory, as this test is considered the in vitro “gold standard.” The performance of laboratories using NT was generally very good, while the laboratories’ performance using other in vitro methods was variable. Laboratories using ELISA and PHA performed less well than those using DAE, dDA-DELFIA, or ToBI. EQA is important for both laboratories that use in vitro nonstandardized methods and those that use commercial ELISA kits

Neonatal invasive disease caused by Streptococcus agalactiae in Europe: the DEVANI multi-center study

peer reviewedPURPOSE Group B streptococcus (GBS) remains a leading cause of invasive disease, mainly sepsis and meningitis, in infants < 3 months of age and of mortality among neonates. This study, a major component of the European DEVANI project (Design of a Vaccine Against Neonatal Infections) describes clinical and important microbiological characteristics of neonatal GBS diseases. It quantifies the rate of antenatal screening and intrapartum antibiotic prophylaxis among cases and identifies risk factors associated with an adverse outcome. METHODS Clinical and microbiological data from 153 invasive neonatal cases (82 early-onset [EOD], 71 late-onset disease [LOD] cases) were collected in eight European countries from mid-2008 to end-2010. RESULTS Respiratory distress was the most frequent clinical sign at onset of EOD, while meningitis is found in > 30% of LOD. The study revealed that 59% of mothers of EOD cases had not received antenatal screening, whilst GBS was detected in 48.5% of screened cases. Meningitis was associated with an adverse outcome in LOD cases, while prematurity and the presence of cardiocirculatory symptoms were associated with an adverse outcome in EOD cases. Capsular-polysaccharide type III was the most frequent in both EOD and LOD cases with regional differences in the clonal complex distribution. CONCLUSIONS Standardizing recommendations related to neonatal GBS disease and increasing compliance might improve clinical care and the prevention of GBS EOD. But even full adherence to antenatal screening would miss a relevant number of EOD cases, thus, the most promising prophylactic approach against GBS EOD and LOD would be a vaccine for maternal immunization.DEVANI: Design of a vaccine to immunize neonates against GBS infections through a durable maternal immune respons