The immunogenicity of seasonal and pandemic influenza vaccination in autoimmune inflammatory rheumatic patients-a 6-month follow-up prospective study.

INTRODUCTION: Influenza may cause severe complications in patients with autoimmune inflammatory rheumatic disease (AIRD), to whom vaccinations are especially recommended. However, AIRD patients require cautious scrutiny of immunogenicity as they might exhibit poor antibody response to vaccination, especially when taking immunomodulatory medications. AIM: The aim was to determine immunogenicity of seasonal and pandemic influenza vaccine in AIRD patients, its timeline/persistence, and influence of medications on immune response. METHODS: One hundred and thirty-seven AIRD and 54 healthy controls were vaccinated with trivalent seasonal influenza. After 3-5 weeks, 15 healthy controls and 93 AIRD were vaccinated with pandemic influenza vaccine, and 63 of patients were vaccinated a second time after 3-5 weeks. Sera were collected before vaccination, 18-90 days after each vaccination, and more than 180 days after the last vaccination. The immune response was measured using hemagglutination inhibition (HI) assay and IgG/IgA antibodies against influenza A/B with ELISA. RESULTS: Our findings indicate that following vaccination with seasonal influenza vaccine, seroprotection, seroresponse, and change in geometric mean titers (GMT) in AIRD patients was not compromised compared to healthy. Similarly, we report for pandemic influenza vaccination little added benefit of the second dose. We confirm lowest increase in HI titer in rituximab-treated AIRD compared to other medications. Vaccination largely tilts the balance from negative ELISA A IgG and IgA titers to positive titers in seasonal H1N1 seroresponsive AIRD patients and controls. A significant decrease in HI GMT and seroprotection was observed only in AIRD at > 180 days after vaccination highlighting an absent persistence of immunogenic response in AIRD patients. Due to high initial HI titers for influenza vaccine, we foresee their benefit in personalized medicine in the future. CONCLUSION: Influenza vaccination is immunologically active for AIRD, with little value of the second dose of the pandemic vaccine and further scrutiny on persistence of immune response to vaccine in AIRD is needed.

Age-specific differences in influenza virus type and subtype distribution in the 2012/2013 season in 12 European countries.

The epidemiology of seasonal influenza is influenced by age. During the influenza season, the European Influenza Surveillance Network (EISN) reports weekly virological and syndromic surveillance data [mostly influenza-like illness (ILI)] based on national networks of sentinel primary-care providers. Aggregated numbers by age group are available for ILI, but not linked to the virological data. At the end of the influenza season 2012/2013, all EISN laboratories were invited to submit a subset of their virological data for this season, including information on age. The analysis by age group suggests that the overall distribution of circulating (sub)types may mask substantial differences between age groups. Thus, in cases aged 5-14 years, 75% tested positive for influenza B virus whereas all other age groups had an even distribution of influenza A and B viruses. This means that the intepretation of syndromic surveillance data without age group-specific virological data may be misleading. Surveillance at the European level would benefit from the reporting of age-specific influenza data.

Estimating seroprevalence of vaccine-preventable infections: is it worth standardizing the serological outcomes to adjust for different assays and laboratories?

The aim of the European Sero-Epidemiology Network 2 (ESEN2) project was to estimate age-specific seroprevalence for a number of vaccine-preventable diseases in Europe. To achieve this serosurveys were collected by 22 national laboratories. To adjust for a variety of laboratory methods and assays, all quantitative results were transformed to a reference laboratory's units and were then classified as positive or negative to obtain age-specific seroprevalence. The aim of this study was to assess the value of standardization by comparing the crude and standardized seroprevalence estimates. Seroprevalence was estimated for measles, mumps, rubella, diphtheria, varicella zoster and hepatitis A virus (HAV) and compared before and after serological results had been standardized. The results showed that if no such adjustment had taken place, seroprevalence would have differed by an average of 3·2% (95% bootstrap interval 2·9-3·6) although this percentage varied substantially by antigen. These differences were as high as 16% for some serosurveys (HAV) which means that standardization could have a considerable impact on seroprevalence estimates and should be considered when comparing serosurveys performed in different laboratories using different assay methods.

Measles virus spread initiated at international mass gatherings in Europe, 2011.

Three parallel transmission chains of measles virus (MV) variant 'D8-Villupuram' (D8-V) originated from two coinciding international mass gathering (MG) events in Rimini, Italy, in June 2011. MV D8-V was independently introduced into Germany by two unvaccinated persons, and into Slovenia by one unvaccinated person who had attended these events. Secondary spread of D8-V was restricted to two generations of transmission in Slovenia as well as in Germany where the virus was further disseminated at another MG. Serological and epidemiological investigation of the D8-V-associated German and Slovenian cases revealed different antibody responses and age distributions. Primary infected young persons between 11 and 27 years-old were affected in Germany, whereas the group of Slovenian cases comprised adults aged from 28 to 47 years and a high proportion (9/14; 64%) of patients with secondary vaccine failure (SVF). Our study demonstrates that monitoring of MV transmission chains in an international context and adequate serological investigation of cases with remote vaccination can contribute to identify susceptibility gaps.

Seroepidemiology of mumps in Europe (1996-2008): why do outbreaks occur in highly vaccinated populations?

Mumps outbreaks have recently been recorded in a number of highly vaccinated populations. We related seroprevalence, epidemiological and vaccination data from 18 European countries participating in The European Sero-Epidemiology Network (ESEN) to their risk of mumps outbreaks in order to inform vaccination strategies. Samples from national population serum banks were collected, tested for mumps IgG antibodies and standardized for international comparisons. A comparative analysis between countries was undertaken using age-specific mumps seroprevalence data and information on reported mumps incidence, vaccine strains, vaccination programmes and vaccine coverage 5-12 years after sera collection. Mean geometric mumps antibody titres were lower in mumps outbreak countries [odds ratio (OR) 0·09, 95% confidence interval (CI) 0·01-0·71)]. MMR1 vaccine coverage ⩾95% remained protective in a multivariable model (P < 0·001), as did an interval of 4-8 years between doses (OR 0·08, 95% CI 0·01-0·85). Preventing outbreaks and controlling mumps probably requires several elements, including high-coverage vaccination programmes with MMR vaccine with 4-8 years between doses.

Safety and efficacy of influenza vaccination in a prospective longitudinal study of 31 children with juvenile idiopathic arthritis.

OBJECTIVES: Influenza vaccination in children with rheumatic diseases is often recommended, but not frequently performed. Our aim was to assess the safety and efficacy of annual influenza vaccination in a longitudinal follow-up study of an unselected group of children with juvenile idiopathic arthritis (JIA). METHODS: Thirty-one children with stable JIA (10 boys, 21 girls, mean age 11.0 years) receiving various therapies and 14 children in a control group (10 boys, 4 girls, mean age 11.9 years) were vaccinated with the annual influenza vaccine Begrivac® 2008/2009. The children in both groups were followed for adverse events and infections 6 months after vaccination. Autoantibodies production and antibody titers against three vaccine viruses were determined in serial samples taken before, 1 and 6 months after vaccination. RESULTS: Eleven (35%) children with JIA and 5 (36%) children in the control group reported short-term adverse events. A JIA flare was observed one month after vaccination in 4 (13%) patients, and in the following five months in 7 (23%) patients. The response to vaccination after one month was significant in the control and study groups as a whole, but not in a subgroup of 4 children receiving anti-TNF-α therapy. After six months, no significant differences in the protective titers against vaccine viruses among the patient and control groups were observed. Changes in the mean values of autoantibodies after vaccination were found only for IgG aCL in the JIA group. CONCLUSIONS: No long-term adverse events were reported after influenza vaccination in JIA and control group. Thirty-five percent of children with JIA experienced flare of the disease after vaccination. Protective antibodies against at least 2 vaccine viruses 6 months after vaccination were detected in all patients.

Influenza A(H1N1) outbreak in a long-term care facility for severely handicapped residents, Slovenia, March-April 2009.

Long-term care facilities are vulnerable to outbreaks of influenza. This report describes the response to such an outbreak in a long-term care facility for severely handicapped children and adults near Ljubljana, Slovenia, in March and April 2009. Of the 23 residents who lived in a unit of the facility, 10 fell ill with fever (>or=37.5 degrees C) during a period of nine days. Probable and confirmed cases were residents who developed a fever after 24 March 2009. Respiratory symptoms were not included in the case definitions as some residents were unable to describe their symptoms due to their mental and/or physical impairment. Epidemiological data were collected and throat and nasal swabs taken. Influenza A virus was identified (without subtyping) and treatment with oseltamivir was given to patients with fever of no more than 48 hours' duration. Oseltamivir was also given prophylactically to healthy residents and staff. Rigorous adherence to standard and droplet precautions was recommended by the regional institute of public health. Two days after respiratory and standard precautions have been strengthened, four more residents became ill. Viral subtyping showed that 12 of the 23 residents were infected with influenza virus A(H1N1); one had an influenza B virus infection. Of the 12 confirmed influenza A cases, 10 had been vaccinated with the seasonal influenza vaccine. Follow-up swabs were taken and were found to be still positive for influenza A virus in 6 of the 12 confirmed cases more then a week after illness onset. The virus was resistant to oseltamivir and susceptible to zanamivir. This influenza outbreak demonstrates the need for rapid typing and subtyping of influenza viruses for accurate diagnosis, treatment and chemoprophylaxis in special settings.

Spotlight on measles 2010: a cluster of measles in a hospital setting in Slovenia, March 2010.

After ten years of being measles free, Slovenia experienced a cluster with secondary transmission in a hospital setting in March 2010. The index case, a resident of Ireland, was hospitalised on the day after his arrival to Slovenia and diagnosed with measles two days later. After his discharge, two cases of measles were notified, a hospital staff member and a visitor to the clinic, suggesting transmission in a hospital setting.

Standardization of measles, mumps and rubella assays to enable comparisons of seroprevalence data across 21 European countries and Australia.

The aim of the European Sero-Epidemiology Network is to establish comparability of the serological surveillance of vaccine-preventable diseases in Europe. The designated reference laboratory (RL) for measles, mumps, rubella (MMR) prepared and tested a panel of 151 sera by the reference enzyme immunoassay (rEIA). Laboratories in 21 countries tested the panel for antibodies against MMR using their usual assay (a total of 16 different EIAs) and the results were plotted against the reference results in order to obtain equations for the standardization of national serum surveys. The RL also tested the panel by the plaque neutralization test (PNT). Large differences in qualitative results were found compared to the RL. Well-fitting standardization equations with R2> or =0.8 were obtained for almost all laboratories through regression of the quantitative results against those of the RL. When compared to PNT, the rEIA had a sensitivity of 95.3%, 92.8% and 100% and a specificity of 100%, 87.1% and 92.8% for measles, mumps and rubella, respectively. The need for standardization was highlighted by substantial inter-country differences. Standardization was successful and the selected standardization equations allowed the conversion of local serological results into common units and enabled direct comparison of seroprevalence data of the participating countries.

Anti-phospholipid antibodies following vaccination with recombinant hepatitis B vaccine.

This study was undertaken to evaluate the possible role of hepatitis B recombinant vaccine inducing the synthesis of IgG and IgM anti-cardiolipin antibodies (aCL), antibodies against beta(2)GPI (anti-beta(2)GPI), lupus anti-coagulant (LA), anti-nuclear antibodies and antibodies against extractable nuclear antigens (anti-ENA). The study population consisted of 85 healthy students (63 female, 22 male; mean age 20.8 years), vaccinated with three doses of recombinant DNA hepatitis B vaccine. One month after vaccination with the first dose of hepatitis B vaccine a minority of vaccinated individuals showed changes in IgG or IgM aCL or anti-beta(2)GPI or LA activity (P < 0.001). Among subjects in whom changes of IgG anti-beta(2)GPI were observed, a significantly higher number of increased (8/85) than decreased (2/85) values were found (P < 0.01). Analyses of paired data showed that differences in aCL or anti-beta(2)GPI levels before vaccination or 1 month later did not reach statistical significance. In two people aCL transitorily reached medium positivity after the first dose of hepatitis B vaccine with a drop 5 months later. Similar evident anti-beta(2)GPI fluctuation was also observed in one person. Another participant was initially low positive for IgG anti-beta2GPI and the levels were increasing after vaccination. Two participants became positive for anti-nuclear antibodies during 6 months' follow-up. There were no sex-dependent differences in tested antibodies observed and no associations between levels of aPL and levels of anti-HBV antibodies. We conclude that HBV can induce aPL, although rarely. In genetically susceptible individuals or together with some other triggers such combination might confer the risk of developing a continuous autoimmune response in an individual.

The seroepidemiology of herpes simplex virus type 1 and 2 in Europe.

OBJECTIVES: To describe the seroepidemiology of herpes simplex virus (HSV) types 1 and 2 in the general populations of eight European countries to better understand recent reported changes in disease epidemiology. METHODS: Belgium, Bulgaria, Czech Republic, England and Wales, Finland, Germany, Netherlands, and Slovenia conducted national cross sectional serological surveys for HSV-1 and HSV-2 between 1989 and 2000. Survey sizes ranged from 3000 to 7166 sera. External quality control was ensured through reference panel testing. RESULTS: Large intercountry and intracountry differences in HSV-1 and HSV-2 seroprevalence were observed. Age standardised HSV-1 seroprevalence ranged from 52% in Finland, to 57% in the Netherlands, 67% in Belgium, 81% in Czech Republic, and 84% in Bulgaria. Age standardised (>12 years) HSV-2 seroprevalence ranged from 24% in Bulgaria, to 14% in Germany, 13% in Finland, 11% in Belgium, 9% in Netherlands, 6% in Czech Republic, and 4% in England and Wales. In all countries, probability of seropositivity for both infections increased with age. A large proportion of teenagers and young adults remain HSV-1 susceptible particularly in northern Europe. Women were significantly more likely to be HSV-2 seropositive in six of seven (p<0.05) countries and HSV-1 seropositive in four of seven (p<0.05) countries, particularly in northern Europe. No significant evidence of a protective role of HSV-1 for HSV-2 infection was found adjusting for age and sex (p<0.05). CONCLUSIONS: There is large variation in the seroepidemiology of HSV-1 and HSV-2 across Europe. The observation that a significant proportion of adolescents are now HSV-1 susceptible may have implications for transmission and clinical presentation of HSV-1 and HSV-2.

Infection of small mammals with Borrelia burgdorferi sensu lato in Slovenia as determined by polymerase chain reaction (PCR).

Thirty-four small mammals collected in the vicinity of Ljubljana were tested for the presence of Borrelia burgdorferi sensu lato by polymerase chain reaction (PCR) of urinary bladder tissues, using universal flagellin primers and species specific rRNA primers. Seventeen small mammals (50%) were found to be positive, and 7 small mammals were infected with two species of B. burgdorferi sensu lato simultaneously. The most commonly found species was B. afzelii (n = 14), followed by B. burgdorferi sensu stricto (n = 7) and B. garinii (n = 3), as determined by species-specific primers. We conclude that PCR is a rapid and reliable method to detect infection with B. burgdorferi sensu lato in small mammals.