European seroepidemiology network 2: Standardisation of assays for seroepidemiology of varicella zoster virus.

BACKGROUND: The aim of the European Sero-Epidemiology Network (ESEN2) is to harmonise the serological surveillance of vaccine-preventable diseases in Europe. OBJECTIVE: To allow comparison of antibody prevalence in different countries by standardising results into common units. STUDY DESIGN: For varicella zoster virus (VZV), a reference laboratory established a panel of 148 samples, characterised by indirect enzyme-immunoassay (ELISA), indirect immunofluorescence, and complement fixation test. Fifty-seven samples were also studied by the fluorescence antibody to membrane antigen test. The geometric mean of the antibody activity (GMAA) obtained from four ELISA determinations was used to characterise each sample of the panel as positive (GMAA: >100 mIU/ml), equivocal (GMAA: 50-100 mIU/ml) or negative (GMAA: <50 mIU/ml) for antibody to VZV (anti-VZV). Thirteen laboratories, using five different ELISA tests, tested the panel. RESULTS: Agreement with the reference laboratory was above 85% in all cases, and the R(2) values obtained from regression analysis of the quantitative results were always higher than 0.87. Finally, the regression equations could be used to convert national values into a common unitage. CONCLUSION: This study confirmed that results for anti-VZV obtained by different ELISA methods can be converted into common units, enabling the comparison of the seroprevalence profiles obtained in the participant countries.     

Persistence of measles, mumps, and rubella antibodies in an MMR-vaccinated cohort: a 20-year follow-up

BACKGROUND: The persistence of antibodies against measles, mumps, and rubella induced by the measles-mumps-rubella (MMR) vaccine and the kinetics of antibody decline after the second MMR vaccine dose were studied in the same cohort for 20 years. METHODS: Measles, mumps, and rubella antibodies were measured by enzyme immunoassay in 20-year follow-up serum samples (n= 183) of twice-vaccinated individuals, and measles antibodies were also measured in oral fluids (n = 177). Antibody decay was determined in a group (n = 58) with subsequent samples collected 1, 8, and 15 years after the second MMR dose. RESULTS: In total, 95%, 74%, and 100% of 183 vaccinees were still seropositive for measles, mumps, and rubella, respectively, and 85% of 177 vaccinees had measurable measles antibodies in their oral fluids. The antibody levels declined significantly after the second dose, but subsequently the rate of decline was slower. CONCLUSIONS: A high rate of seropositivity was found 20 years after the first MMR dose, particularly for rubella and measles. Our results show that MMR vaccine-induced antibodies wane significantly after the second dose. According to epidemiological data, the protection induced by MMR vaccination in Finland seems to persist at least until early adulthood. However, the situation requires constant vigilance.     

How many third molars remain unnoticed in a population survey without panoramic radiographs?

Clinical Oral Investigations - The aim of the study was to compare the findings of clinical examination and panoramic radiograph regarding the occurrence of third molars in a population survey to...     

Mental health service users’ experiences of an education intervention based on a European Union project: A comparison between nine European countries

Mental health service users (MHSUs) often face difficulties in achieving successful participation in education; however, the tools that could help them succeed are rarely investigated. This study aimed to illuminate the experiences of MHSUs in an education intervention based on a European Union (EU) project. Their experiences are compared across nine EU countries. The data were collected through individual interviews with MHSUs (n = 47) at day activity centres that provide mental health services. An inductive content analysis was used as the method of analysis. Three main categories, which include seven subcategories, are revealed by the analysis. The main categories are as follows: (i) the factors related to MHSUs’ educational preparedness, (ii) the dimensions of the learning environment, and (iii) the effects of training intervention. The MHSUs’ experiences with the education intervention were similar across all countries. The findings showed that this education intervention is a multidimensional process. It contains social, mental, and physical dimensions linked to a learner and learning environment. These dimensions influence the MHSUs’ ability to participate in the education process. At its best, the education intervention supports the personal growth of MHSUs and prepares them for social integration. An education intervention can be a usable tool in the rehabilitation of MHSUs if the multidimensional nature of education is taken into consideration. Therefore, designing and executing education interventions requires the attendance of the MHSUs in cooperation with mental health and education professionals. Our findings suggest a tentative framework that can be used in designing and executing education for MHSUs.     

Current management of late onset neonatal bacterial sepsis in five European countries

Late onset neonatal sepsis (LOS) has a high mortality and the optimal management is poorly defined. We aimed to evaluate new expert panel-derived criteria to define LOS and characterize the current management and antibiotic susceptibility of LOS-causing organisms in Europe. A prospective observational study enrolled infants aged 4 to 90 days in five European countries. Clinical and laboratory findings as well as empiric treatment were recorded and patients were followed until the end of antibiotic therapy. Failure was defined as a change of primary antibiotic, no resolution of clinical signs, appearance of new signs/pathogens or death. Antibiotic therapy was considered appropriate if the organism was susceptible to at least one empiric antibiotic. 113 infants (median age 14 days, 62 % ≤1500 g) were recruited; 61 % were culture proven cases (28 CoNS, 24 Enterobacteriaceae, 11 other Gram-positives and 6 Gram-negative non-fermentative organisms). The predictive value of the expert-panel criteria to identify patients with a culture proven LOS was 61 % (95 % CI 52 % to 70 %). Around one third of Enterobacteriaceae were resistant to ampicillin + or cefotaxime + gentamicin but only 10 % to meropenem. Empiric treatment contained a total of 43 different antibiotic regimens. All-cause mortality was 8 % with an additional 45 % classified as failure of empiric therapy, mainly due to change of primary antibiotics (42/60). Conclusions: The expert panel—derived diagnostic criteria performed well identifying a high rate of culture proven sepsis. Current management of LOS in Europe is extremely variable suggesting an urgent need of evidence-based guidelines.     

Immunogenicity and safety of a combined hepatitis A and B vaccine administered concomitantly with either a measles-mumps-rubella or a diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine mixed with a Haemophilus influenzae type b conjugate vaccine in infants aged 12-18 months

Two studies were undertaken to investigate the concomitant administration of combined hepatitis A/B vaccine with a diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis vaccine mixed with Haemophilus influenzae vaccine (DTPa-IPV/Hib), or with a measles-mumps-rubella vaccine (MMR), during the second year of life. On completion of the vaccination course, all subjects were seropositive or seroprotected against all antigens except for one subject who was seronegative for anti-PT. Seropositivity and seroprotection rates for all other antibodies were comparable to reference values for each vaccine component, indicating that the immunogenicity of MMR, DTPa-IPV/Hib and combined hepatitis A/B vaccines is not impaired by co-administration. All vaccines were well tolerated.     

A fragment of histidine-rich glycoprotein is a potent inhibitor of tumor vascularization

In this study, we show that recombinant human histidine-rich glycoprotein (HRGP) has potent antiangiogenic properties as judged from effects on a syngeneic tumor model in C57/bl6 mice. Growth of fibrosarcoma, a very aggressive tumor, was reduced by >60% by HRGP treatment, and tumor angiogenesis was dramatically decreased. Treatment with HRGP led to increased apoptosis and reduced proliferation in the tumors. In contrast, HRGP did not affect apoptosis or DNA synthesis in endothelial cells or tumor cells in vitro. The mechanism of action of HRGP involves rearrangement of focal adhesions and decreased attachment of endothelial cells to vitronectin and, as a consequence, reduced endothelial cell migration. By using truncated versions of HRGP, we demonstrate that the isolated 150 amino acid-residue His/Pro-rich domain, which is also released by spontaneous proteolysis from purified HRGP, mediates the inhibitory effect on chemotaxis. Moreover, the His/Pro-rich domain must be released from HRGP to exert its effect. This study shows for the first time inhibitory effects of HRGP on tumor vascularization in vivo, thus providing proof of concept that HRGP is an angiogenesis inhibitor.     

IgG avidity to distinguish secondary from primary measles vaccination failures: prospects for a more effective global measles elimination strategy

The nearly 40-year long debate on the relevance of secondary measles vaccination failure has been inconclusive because a feasible method for the assessment of the duration of immunity has been lacking. Even if a two-dose measles vaccination policy is now universally endorsed, WHO still officially adheres to the view that a single successful measles vaccination, without natural boosters, induces a lifelong immunity and deems secondary failures epidemiologically irrelevant - in the belief that the latter are rare and do not participate in the transmission chain. A recently published study on measles-IgG avidity, which allows for separation of secondary from primary vaccination failures, tentatively showed that the official view does not necessarily hold true. The results may have wide implications on global measles eradication efforts. The potential of IgG avidity measurement in complex postvaccination measles epidemiology is discussed.     

Buffy coat PCR for diagnosis of experimental pneumococcal pneumonia

An immunocompetent murine model of pneumococcal pneumonia and bacteremia was used to evaluate a PCR assay based on amplification of the pneumolysin gene. Mice were treated with trovafloxacin to determine the decline in sensitivity of PCR as lung bacterial concentrations decreased and blood cultures became sterile. Forty-three mice were studied for up to 120 h after start of antibiotic treatment. PCR of buffy coat specimens was more sensitive than PCR of plasma. Only 21% of animals had a positive blood culture, whereas 77% of PCR buffy coat assays were positive. After 48 h of therapy all blood culture specimens were sterile, whereas buffy coat PCR was positive in 57.8% of specimens. PCR of buffy coat specimens was negative in all mice colonized nasally with Streptococcus pneumoniae and in rabbits with Escherichia coli bacteremia. Our results demonstrate that our PCR technique using buffy coat specimens is highly specific for invasive pneumococcal disease and remains positive in the majority of animals for at least 48 h after start of antibiotic therapy.     

Pharmacodynamics of vancomycin for the treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis

With the emergence of beta-lactam antibiotic resistance among strains of Streptococcus pneumoniae, vancomycin has assumed an important role in the treatment of bacterial meningitis. Using the rabbit meningitis model, we evaluated the pharmacokinetics and pharmacodynamics of vancomycin in this setting. Animals were given 80 mg/kg of body weight daily in two or four divided doses to determine the penetration and activity of vancomycin in cerebrospinal fluid (CSF); each regimen was administered with and without dexamethasone. Mean peak (2 h) concentrations in CSF that were four- to eightfold higher than the minimum bactericidal concentration (MBC; 0.5 microgram/ml) for the pathogen were adequate for bacterial clearance. In both groups concentrations in CSF remained higher than the MBC for greater than 80% of the respective dosing intervals, and the penetration of vancomycin into CSF was 20%. Mean concentrations in CSF at 24 to 36 h of therapy were lower than those achieved during the first 12 h, consistent with a decline in the level of antibiotic entry into CSF as inflammation wanes. Rates of bacterial clearance were similar for the two regimens, and for all animals cultures of CSF were sterile by 36 h. The coadministration of dexamethasone significantly reduced the penetration of vancomycin into CSF by 29% and significantly lowered the rate of bacterial clearance during the first 6 h in animals receiving 20-mg/kg doses of vancomycin. For animals receiving 40-mg/kg doses, therapeutic peak concentrations in CSF were obtained even with steroid use, suggesting that the effect of steroids may be circumvented by the use of larger daily doses of vancomycin.