[Tick-Borne Encephalitis (TBE) - Fundamentals]. / Frühsommer-Meningoenzephalitis (FSME).

Tick-Borne Encephalitis (TBE) - Fundamentals Abstract. There is widespread endemicity of tick-borne encephalitis (TBE) in all German-speaking countries. In most regions there is a gradual increase in incidence and further territorial spread. As a proportion of the cases is not diagnosed and since the clinical course is getting worse with growing age, substantial underreporting occurs particularly in the pediatric and adolescent patient population. Infected ticks are transmitting the TBE virus, a flavivirus, within a few minutes after the bite. After an incubation period of 4 to 28 days uncharacteristic flu-like symptoms usually occur during a first viremic phase. This is followed by a brief asymptomatic interval before a minority of patients suffer of a variety of symptoms associated with damage of different parts of the central nervous system. This often results in permanent neurological injury and in about 1% the clinical course is fatal. To establish a diagnosis, it is essential to suspect the infection and to obtain a history of exposure. Depending on the phase of illness IgM and/or IgG antibodies can be detected in the serum and/or in the cerebrospinal fluid. In the early phase of the infection the TBE virus may be detected by PCR.

Antibody seroprevalence and rate of asymptomatic infections with SARS-CoV-2 in Austrian hospital personnel.

BACKGROUND: The aims of this study are to determine (i) SARS-CoV-2 antibody positive employees in Austrian trauma hospitals and rehabilitation facilities, (ii) number of active virus carriers (symptomatic and asymptomatic) during the study, (iii) antibody decline in seropositive subjects over a period of around 6 months, (iv) the usefulness of rapid antibody tests for outpatient screening. METHOD: A total of 3301 employees in 11 Austrian trauma hospitals and rehabilitation facilities of the Austrian Social Insurance for Occupational Risks (AUVA) participated in this open uncontrolled prospective cohort study. Rapid lateral flow tests, detecting a combination of IgM and IgM against SARS-CoV-2), two different types of CLIA (Diasorin, Roche), RT-PCR tests and serum neutralization tests (SNTs) were performed. The tests were conducted twice, with an interval of 42.4 ± 7.7 (Min = 30, Max = 64) days. Positive participants were re-tested with CLIA/SNT at a third time point after 188.0 ± 12.8 days. RESULTS: Only 27 out of 3301 participants (0.82%) had a positive antibody test at any time point during the study confirmed via neutralization test. Among positively tested participants in either test, 50.4% did not report any symptoms consistent with common manifestations of COVID-19 during the study period or within the preceding 6 weeks. In the group who tested positive during or prior to study inclusion the most common symptoms of an acute viral illness were rhinitis (21.9%), and loss of taste and olfactory sense (21.9%). Based on the neutralization test as the true condition, the rapid antibody test performed better on serum than whole blood as 84.6% instead of 65.4% could be detected correctly. Concerning both CLIA tests overall the Roche test detected 24 (sensitivity = 88.9%) and the Diasorin test 22 positive participants (sensitivity = 81.5%). In participants with a positive SNT result, a significant drop in neutralizing antibody titre from 31.8 ± 22.9 (Md = 32.0) at T1 to 26.1 ± 17.6 (Md = 21.3) at T2 to 21.4 ± 13.4 (Md = 16.0) at T3 (χ2 = 23.848, df = 2, p < 0.001) was observed (χ2 = 23.848, df = 2, p < 0.001)-with an average time of 42.4 ± 7.7 days between T1 and T2 and 146.9 ± 13.8 days between T2 and T3. CONCLUSIONS: During the study period (May 11th-August 3rd) only 0.82% were tested positive for antibodies in our study cohort. The antibody concentration decreases significantly over time with 14.8% (4 out of 27) losing detectable antibodies.

Vaccination in Multiple Sclerosis: Friend or Foe?

Multiple sclerosis (MS) is a debilitating disease of the central nervous systems (CNS). Disease-modifying treatments (including immunosuppressive treatments) have shown positive effects on the disease course, but are associated with systemic consequences on the immune system and may increase the risk of infections and alter vaccine efficiency. Therefore, vaccination of MS patients is of major interest. Over the last years, vaccine hesitancy has steadily grown especially in Western countries, partly due to fear of sequelae arising from vaccination, especially neurological disorders. The interaction of vaccination and MS has been discussed for decades. In this review, we highlight the immunology of vaccination, provide a review of literature and discuss the clinical consideration of MS, vaccination and immunosuppression. In conclusion, there is consensus that MS cannot be caused by vaccines, neither by inactivated nor by live vaccines. However, particular attention should be paid to two aspects: First, in immunocompromised patients, live vaccines may lead to a stronger immune reaction with signs of the disease against which the patients have been vaccinated, albeit in weakened form. Second, protection provided by vaccination should be controlled in patients who have been vaccinated while receiving immunomodulatory or immunosuppressive treatment. In conclusion, there is evidence that systemic infections can worsen MS, thus vaccination will lower the risk of relapses by reducing the risk of infections. Therefore, vaccination should be in general recommended to MS patients.

Persistence of the immune response after vaccination with the Japanese encephalitis vaccine, IXIARO® in healthy adults: A five year follow-up study.

Immunization with the Japanese encephalitis (JE) vaccine IXIARO® results in protective neutralizing antibody levels for one year. Since persistence of protective titer levels beyond one year was unknown, a 5 years follow-up study was conducted. Additionally, data were stratified to compare the persistence of protective neutralizing antibodies against JE in people with or without tick-borne encephalitis (TBE) vaccination. Four weeks after the primary series, the percentage of subjects with PRNT50 titer ≥1:10 in the intent-to-treat population was 99%; the rate after 5 years was 81.6%. By month 24, 36, 48 and 60, the percentages were still 90.7%, 91.7%, 90.1%, 85.9%, respectively in the population who had received TBE vaccine compared to 67.9%, 71.9%, 69.1%, 63.8% in the population who had not. No long-term safety concerns were identified. These data indicate that vaccination with IXIARO® is able to induce protective titers that persist up to 60 months after the primary immunization. Clinical trial registry number NCT00596102.

Age-related differences in humoral and cellular immune responses after primary immunisation: indications for stratified vaccination schedules.

Immunosenescence is characterised by reduced B and T cell responses. Evidence shows that booster vaccinations are less effective in elderly people, but data on the efficacy of primary immunisation are sparse. We conducted a monocentric, open label, phase IV trial to compare immune responses to primary vaccinations using the inactivated, adjuvanted Japanese Encephalitis vaccine by 30 elderly people (mean 69, range 61-78 years) and 30 younger people (mean 24, range 18-30 years). Humoral and cellular immune responses were analysed in relation to age and cytomegalovirus (CMV) seropositivity. Vaccine-specific antibody titres were significantly lower in elderly participants and 47% of them were non- or low responders after the two doses of the vaccine neo-antigen. The reduced humoral immune responses in elderly people correlated with reduced cytokine production, such as interferon gamma (IFN-γ) in vitro, as well as higher frequencies of late-differentiated effector and effector memory T cells and T regulatory cells. These cellular changes and lower antibody titres were particularly prominent in CMV-seropositive elderly participants. If primary vaccination before the age of 60 is not possible, elderly patients may require different vaccination strategies to ensure sufficient long-lasting immunity, such as adapted or accelerated schedules and the use of different adjuvants.

Immunogenicity and safety of the inactivated Japanese encephalitis vaccine IXIARO® in elderly subjects: Open-label, uncontrolled, multi-center, phase 4 study.

BACKGROUND: IXIARO® is a Vero cell-derived, inactivated Japanese encephalitis (JE) vaccine licensed mainly in western countries for children and adults traveling to JE endemic areas. Limited immunogenicity and safety data in elderly travelers have been available. OBJECTIVES: To evaluate safety and immunogenicity of IXIARO in elderly subjects. METHODS: Open-label, single arm, multi-centered study. Two-hundred subjects with good general health, including adequately controlled chronic conditions, received two doses of IXIARO®, 28days apart. Protective levels of antibodies were tested 42days after the second dose. Systemic and local adverse events (AEs) were solicited for 7days after each dose, unsolicited AEs were collected up to day 70 and in a phone call at month 7. SUMMARY OF RESULTS: Subjects were aged 64-83years (median 69.0years). Nineteen percent of subjects had serious or medically attended AEs up to Day 70 (primary endpoint), none of them causally linked to IXIARO. Solicited local AEs were reported by 33.5% (most common: local tenderness) and solicited systemic AEs by 27% (most common: headache) of subjects. The seroprotection rate was 65% with a geometric mean titre (GMT) of 37. Subjects with tick borne encephalitis (TBE) vaccinations in the past 5years (N=29) had a SCR of 90% and GMT of 65. CONCLUSIONS: IXIARO is generally well tolerated in the elderly, and the safety profile is largely comparable with younger adults. SCR and GMT are lower compared to younger adults, but SCR is in the range reported in elderly for other vaccines e.g. against TBE, hepatitis-A virus (HAV)/hepatitis-B virus (HBV), influenza. The differences in SCR and GMT from younger to elderly adults were in the range of other vaccines. Duration of protection is uncertain in older persons, therefore a booster dose (third dose) should be considered before any further exposure to JE virus.

[Guidelines for vaccination of immunocompromised individuals]. / Impfungen bei Immundefekten/Immunsuppression - Expertenstatement und Empfehlungen.

Immunosuppression of various origins is associated with an increased risk of infection; therefore the prevention of infectious diseases by vaccination is especially important in immunocompromised patients. However, the response to vaccinations is often reduced in these risk groups and the application of live vaccines is contraindicated during immunosuppression.In the following expert statement, recommendations for vaccination were created on the basis of current evidence and theoretical/immunological considerations. A first, general part elaborates on efficacy and safety of vaccinations during immunosuppression, modes of action of immunosuppressive medications and recommended time intervals between immunosuppressive treatments and vaccinations. A core piece of this part is a graduation of immunosuppression into three stages, i. e. no relevant immunosuppression, mild to moderate and severe immunosuppression and the assignment of various medications (including biologicals) to one of those stages; this is followed by an overview of possible and necessary vaccinations in each of those stages.The second part gives detailed vaccination guidelines for common diseases and therapies associated with immunosuppression. Primary immune deficiencies, chronic kidney disease, diabetes mellitus, solid and hematological tumors, hematopoetic stem cell transplantation, transplantation of solid organs, aspenia, rheumatological-, gastroenterologic-, dermatologic-, neurologic diseases, biologicals during pregnancy and HIV infection are dealt with.These vaccination guidelines, compiled for the first time in Austria, aim to be of practical help for physicians to facilitate and improve vaccination coverage in immunocompromised patients and their household members and contact persons.

Genetic Variation of Bordetella pertussis in Austria.

In Austria, vaccination coverage against Bordetella pertussis infections during infancy is estimated at around 90%. Within the last years, however, the number of pertussis cases has increased steadily, not only in children but also in adolescents and adults, indicating both insufficient herd immunity and vaccine coverage. Waning immunity in the host and/or adaptation of the bacterium to the immunised hosts could contribute to the observed re-emergence of pertussis. In this study we therefore addressed the genetic variability in B. pertussis strains from several Austrian cities. Between the years 2002 and 2008, 110 samples were collected from Vienna (n = 32), Linz (n = 63) and Graz (n = 15) by nasopharyngeal swabs. DNA was extracted from the swabs, and bacterial sequence polymorphisms were examined by MLVA (multiple-locus variable number of tandem repeat analysis) (n = 77), by PCR amplification and conventional Sanger sequencing of the polymorphic regions of the prn (pertactin) gene (n = 110), and by amplification refractory mutation system quantitative PCR (ARMS-qPCR) (n = 110) to directly address polymorphisms in the genes encoding two pertussis toxin subunits (ptxA and ptxB), a fimbrial adhesin (fimD), tracheal colonisation factor (tcfA), and the virulence sensor protein (bvgS). Finally, the ptxP promoter region was screened by ARMS-qPCR for the presence of the ptxP3 allele, which has been associated with elevated production of pertussis toxin. The MLVA analysis revealed the highest level of polymorphisms with an absence of MLVA Type 29, which is found outside Austria. Only Prn subtypes Prn1/7, Prn2 and Prn3 were found with a predominance of the non-vaccine type Prn2. The analysis of the ptxA, ptxB, fimD, tcfA and bvgS polymorphisms showed a genotype mixed between the vaccine strain Tohama I and a clinical isolate from 2006 (L517). The major part of the samples (93%) displayed the ptxP3 allele. The consequences for the vaccination strategy are discussed.

Persistence of antibodies six years after booster vaccination with inactivated vaccine against Japanese encephalitis.

BACKGROUND: Japanese Encephalitis (JE) virus occurs in wide regions of Asia with over 3 billion people living in areas at risk for JE. An estimated 68,000 clinical cases of JE occur every year, and vaccination is the most effective prophylactic measure. One internationally licensed vaccine containing the inactivated JE virus strain SA14-14-2 is Ixiaro (Valneva, Austria). According to recommendations, basic immunization consists of vaccinations on day 0, day 28, and a booster dose 12-24 months later. Protection in terms of neutralizing antibody titers has been assessed up to 12 months after the third dose of the vaccine. The current investigation was designed to evaluate antibody decline over time and to predict long-term duration of seroprotection after a booster dose. METHOD: In a preceding trial, volunteers received basic immunization (day 0, day 28) and one booster dose against JE 15 months later. A follow up blood draw 6 years following their booster dose was carried out in 67 subjects. For antibody testing, a 50% plaque reduction neutralization test (PRNT50-test) was used. PRNT50 values of 10 and above are surrogate levels of protection according to WHO standards. RESULT: Seventy-six months following the booster dose, 96% of the tested subjects had PRNT50 titers of 10 or higher. Geometric mean titer (GMT) was 148 (95% CI confidence interval: 107-207). Antibody titers were lower in volunteers 50 years of age and older. Vaccination history against other flaviviruses (yellow fever or tick borne encephalitis) did not significantly influence PRNT50 titers. A two-step log-linear decline model predicted protection against JE of approximately 14 years after the booster dose. CONCLUSION: Six years after a booster dose against JE, long-term protection could be demonstrated. According to our results, further booster doses should be scheduled 10 years following the first booster dose.

A Novel multivalent OspA vaccine against Lyme borreliosis is safe and immunogenic in an adult population previously infected with Borrelia burgdorferi sensu lato.

Lyme borreliosis (LB) patients who recover, as well as previously infected asymptomatic individuals, remain vulnerable to reinfection with Borrelia burgdorferi sensu lato. There is limited information available about the use of OspA vaccines in this population. In this study, a randomized double-blind phase I/II trial was performed to investigate the safety and immunogenicity of a novel multivalent OspA vaccine in healthy adults who were either seronegative or seropositive for previous B. burgdorferi sensu lato infection. The participants received three monthly priming immunizations with either 30 µg or 60 µg alum-adjuvanted OspA antigen and a booster vaccination either 6 months or 9 to 12 months after the first immunization. The antibody responses to the six OspA serotypes included in the vaccine were evaluated. Adverse events were predominantly mild and transient and were similar in the seronegative and seropositive populations. Substantial enzyme-linked immunosorbent assay (ELISA) and surface-binding antibody responses against all six OspA antigens were induced after the primary immunization schedule in both populations, and they were substantially increased with both booster schedules. The antibody responses induced by the two doses were similar in the seronegative population, but there was a significant dose response in the seropositive population. These data indicate that the novel multivalent OspA vaccine is well tolerated and immunogenic in individuals previously infected with B. burgdorferi sensu lato. (This study is registered at ClinicalTrials.gov under registration no. NCT01504347.).

Safety and immunogenicity of modified vaccinia Ankara as a smallpox vaccine in people with atopic dermatitis.

BACKGROUND: Following vaccination with traditional smallpox vaccines or after exposure to vaccinated individuals, subjects with atopic dermatitis (AD) can develop eczema vaccinatum, a severe disease with disseminated eruption of pustular contagious lesions. Alternative smallpox vaccines with an improved safety profile would address this unmet medical need. METHODS: An open-label controlled Phase I clinical trial was conducted to investigate the safety and immunogenicity of modified vaccinia Ankara (MVA) in 15 healthy subjects compared to 45 subjects with either mild allergic rhinitis, a history of AD or presenting with mild active AD. MVA was given (Week 0 and 4) by a subcutaneous injection during a 28-week observation period. RESULTS: No serious adverse event was reported and vaccinations with MVA did not lead to any clinically relevant skin reactions in AD subjects. Unsolicited administration site reactions did not show any trends compared to the healthy subject group. The majority of adverse reactions were mild to moderate, and all reactions were transient and resolved without intervention. The majority of vaccinees had seroconverted by ELISA (80-93%) and PRNT (69-79%) already two weeks after the first vaccination, increasing to 100% after the second immunization, with peak GMT above 1000 and 145 for ELISA and PRNT, respectively. CONCLUSIONS: MVA was equally well tolerated and immunogenic in all enrolled subjects with mild to moderate pain and redness at the injection site being the most frequent adverse reactions. There were no differences in the safety or immunogenicity profile of MVA in healthy subjects or those with AD or allergic rhinitis. The study has confirmed MVA as a promising smallpox vaccine candidate and demonstrated in a small study population that the vaccine has a similar safety and immunogenicity profile in healthy subjects and people with active AD. CLINICAL TRIALS REGISTRATION: NCT00189917.

Characteristics of invasive pneumococcal disease in hospitalized children in Austria.

UNLABELLED: In a prospective surveillance study covering all pediatric wards in Austria, 308 cases of invasive pneumococcal disease (IPD) were reported in hospitalized children <5 years of age between 2002 and 2012. Incidence was 7.1 per 100,000 per year for IPD with a case fatality rate of 3 %, and 1.9 per 100,000 per year for pneumococcal meningitis with a case fatality rate of 9 %. At hospital discharge, 17 % of the children were not fully recovered and suffered from problems such as hearing or motor deficits. Persistent sequelae 6 months after hospital discharge were present in 13 % of the children, a finding that emphasizes the seriousness of IPD. From 2007 onwards, we observed a shift of pneumococcal serotypes from those covered by the heptavalent vaccine to serotypes consequently added to 10- and 13-valent vaccines, particularly regarding serotype 19A. Among antimicrobial resistances detected, macrolide resistance was predominant; however, between 2002 and 2012, we saw an overall decrease of resistance rates. CONCLUSION: Considering this change of serotypes and the high rate of permanent sequelae after IPD, our data show the importance of pediatric pneumococcal vaccination and the relevance of continuous monitoring of circulating serotypes. By the end of 2012, which was the first year of universal mass vaccination against pneumococcal disease in Austria, no change in the incidence of invasive pneumococcal disease was observed yet.

[Vaccination recommendations for health care workers in Austria]. / Impfungen für Mitarbeiter des Gesundheitswesens.

In Austria the vaccination coverage among health care workers (HCW) - particularly among hospital personnel - is not sufficient. This is of specific concern, because not only the individual protection but also the prevention of disease transmission of vaccine preventable diseases between HCW and patients needs to be guaranteed. Particularly immunosuppressed patients, who are at higher risk for morbidity and mortality due to certain infections, but cannot be vaccination themselves, must be able to rely on herd protection, i.e. not being infected by surrounding/caring persons. The following publication provides for the first time detailed guidelines for vaccination programs for HCWs in Austria, including personnel within hospitals, medical institutions and laboratories, as well as Medical Universities including students. Moreover, these guidelines are also recommended to medical personnel in outpatient clinics, social service institutions and medical practices. Additionally to the vaccination schedules this publication also includes a chapter on ethical as well as legal background underlying these recommendations.

Gender-specific distribution of mefloquine in the blood following the administration of therapeutic doses.

BACKGROUND: The objectives of the study were to elucidate the gender-specific distribution of mefloquine in cellular and fluid blood compartments when given at therapeutic dosage, to assess its correlation with the occurrence of treatment-related adverse events, and to explore the necessity of adjusting treatment guidelines for females. METHODS: The distribution of mefloquine following the administration of standard therapeutic doses (1,250 mg mefloquine in split dose) to 22 healthy Caucasian volunteers was assessed in whole blood, serum, plasma, red blood cells (RBCs), white blood cells, and platelets using high performance liquid chromatography. RESULTS: Plasma mefloquine concentrations after 14 hours were considerably higher in female subjects than in males (2,778 vs 1,017 ng/ml at H14), concordant with a significantly higher frequency, duration, and severity of adverse reactions. However, mean drug concentrations of RBC appeared slightly higher in male volunteers (857 vs 719 ng/ml). At H48, a similar situation prevailed, and at H168 the mefloquine concentrations in plasma continued to be higher in females compared to males (1,353 vs 666 ng/ml), while the concentrations of RBC were similar in females (389 vs 375 ng/ml). Since the observations relate to healthy individuals, they do not take into account selective uptake of mefloquine by Plasmodium-infected erythrocytes as in the case of therapeutic drug use. CONCLUSION: Although plasma mefloquine concentrations in female healthy volunteers are considerably higher and the concentrations of the RBCs are initially lower compared to males, they do not seem to justify an adjustment of treatment guidelines for mefloquine in female Caucasian individuals.

Tick-borne encephalitis (TBE) and hepatitis B nonresponders feature different immunologic mechanisms in response to TBE and influenza vaccination with involvement of regulatory T and B cells and IL-10.

Low responsiveness/nonresponsiveness is characterized by an insufficient immune response upon primary and/or booster vaccination and affects 1-10% of vaccinees. In the current study, we aimed to investigate whether nonresponsiveness is an Ag/vaccine-specific phenomenon and to clarify underlying immunological mechanisms. Nonresponders to tick-borne encephalitis (TBE) or hepatitis B Ag with a history of previous TBE vaccinations were booster vaccinated with TBE and influenza vaccine and compared with TBE high responders in terms of humoral and cellular immune response. Postboosters in TBE high responder existing TBE titers increased, and solid humoral responses to influenza vaccine were induced. In TBE nonresponders, low to undetectable prevaccination TBE titers remained low, whereas sufficient influenza Abs were induced. In both TBE groups, a positive correlation of humoral and cellular immune response was seen as high/low TBE titers were associated with sufficient/lack of Ag-specific T cell proliferation. Furthermore, responses to influenza were robust in terms of Abs and cytokine production. In contrast, in hepatitis B nonresponders, sufficient humoral responses to TBE and influenza Ags were induced despite lacking specific IL-2 and IFN-γ production. Importantly, these patients showed high IL-10 baseline levels in vitro. HLA-DR subtypes associated with hepatitis B nonresponsiveness were overrepresented in this group, and high IL-10 levels were linked to these subtypes. Whereas TBE and hepatitis B nonresponders had increased IL-10-producing FOXP3(+) T regulatory cells upon vaccination, only in hepatitis B nonresponders, showing elevated prevaccination IL-10 levels, a prominent population of B regulatory cells was detected. We conclude that immunological pathways of nonresponsiveness follow different patterns depending both on vaccine Ag and genetic predisposition of the vaccinee.

Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial.

BACKGROUND: Lyme borreliosis is caused by Borrelia burgdorferi sensu stricto in the USA and by several Borrelia species in Europe and Asia, but no human vaccine is available. We investigated the safety and immunogenicity of adjuvanted and non-adjuvanted vaccines containing protective epitopes from Borrelia species outer surface protein A (OspA) serotypes in healthy adults. METHODS: Between March 1, 2011, and May 8, 2012, we did a double-blind, randomised, dose-escalation phase 1/2 study at four sites in Austria and Germany. Healthy adults aged 18-70 years who were seronegative for B. burgdorferi sensu lato were eligible for inclusion. Participants were recruited sequentially and randomly assigned to one of six study groups in equal ratios via an electronic data capture system. Participants and investigators were masked to group allocation. Participants received three vaccinations containing 30 µg, 60 µg, or 90 µg OspA antigen with or without an adjuvant, with intervals of 28 days, and a booster 9-12 months after the first immunisation. The coprimary endpoints were the frequency and severity of injection-site and systemic reactions within 7 days of each vaccination, and the antibody responses to OspA serotypes 1-6, as established by ELISA. This study is registered with ClinicalTrials.gov, number NCT01504347. FINDINGS: 300 participants were randomly assigned: 151 to adjuvanted vaccines (50 to 30 µg, 51 to 60 µg, and 50 to 90 µg doses), and 149 to non-adjuvanted vaccines (50 to 30 µg, 49 to 60 µg, and 50 to 90 µg doses). Adverse reactions were predominantly mild, and no vaccine-related serious adverse events were reported. The risk of systemic reactions (risk ratio 0·54 [95% CI 0·41-0·70]; p<0·0001) and of moderate or severe systemic reactions (0·35 [0·13-0·92]; p=0·034) was significantly lower for adjuvanted than non-adjuvanted formulations. The 30 µg adjuvanted formulation had the best tolerability profile; only headache (five [10%, 95% CI 4-20] of 50), injection-site pain (16 [32%, 21-45]), and tenderness (17 [34%, 23-47]) affected more than 6% of patients. All doses and formulations induced substantial mean IgG antibody titres against OspA serotypes 1-6 after the first three vaccinations (range 6944-17,321) and booster (19,056-32,824) immunisations. The 30 µg adjuvanted formulation induced the highest antibody titres after the booster: range 26,143 (95% CI 18,906-36,151) to 42,381 (31,288-57,407). INTERPRETATION: The novel multivalent OspA vaccine could be an effective intervention for prevention of Lyme borreliosis in Europe and the USA, and possibly worldwide. Larger confirmatory formulation studies will need to be done that include individuals seropositive for Borrelia burgdorferi sensu lato before placebo-controlled phase 3 efficacy studies can begin. FUNDING: Baxter.

Sustained low hospitalization rates after four years of rotavirus mass vaccination in Austria.

This hospital based surveillance study evaluates the effects of the rotavirus mass vaccination program, which was initiated in Austria in August 2007. Since then, incidence rates of rotavirus hospitalizations in children <15 years of age have decreased by 70% and 64% in 2010 and 2011 compared to the pre-vaccination era (2001-2005). Incidence rates were highest in children <90 days of age, highlighting the importance of the early start of active rotavirus immunization. In children between 2 and 3.5 years in 2011, who were in the second and third year after vaccination in the universal mass vaccination program, incidence rates remained low suggesting sustained protection after vaccination up to three years. In the years 2010 and 2011, field effectiveness of the vaccines was between 79% and 96%, depending on the assumptions made for children without information on vaccination history. From genotyping an increase of the prevalence of G2P[4] in children with breakthrough infection (disease despite vaccination) can be suspected. The rate of severe adverse events was 1.3-1.5 per 10(-5) administered doses of rotavirus vaccines and no death, intussusception or Kawasaki disease was reported in 2010 and 2011 following rotavirus vaccination.

Factors associated with seroimmunity against tick borne encephalitis virus 10 years after booster vaccination.

In a sample of originally 430 healthy adults (18-84 years of age) with documented basic and booster immunization against tick borne encephalitis, cumulative seroprotection rates 8 (n=178) and 10 years (n=183) after the last booster dose were 86.8% and 77.3% according to the neutralization test, respectively. In subjects aged 50 years and older, antibody titers were significantly lower compared to subjects younger than 50 years. History of any allergy but not previous exposure to other flaviviral antigens was associated with higher neutralization titers. In subjects with waning immunity, a single booster dose induced a strong anamnestic antibody response.

Vaccines and vaccination against tick-borne encephalitis.

Tick-borne encephalitis (TBE) is an emerging viral zoonosis and is endemic from Japan, China, Mongolia and Russia, to Central Europe and France. There is no specific treatment and TBE can be fatal. The four licensed prophylactic vaccines are produced according to WHO manufacturing requirements. Large clinical trials and postmarketing surveillance demonstrated safety and efficacy of the two European vaccines. The two Russian vaccines showed their effectiveness in daily use, but limited published data are available on controlled clinical trials. Vaccination recommendations in endemic areas vary significantly. In some countries, public vaccination programs are implemented. The WHO has recently issued recommendations on evidence-based use of TBE vaccines. However, more data are needed regarding safety, efficacy and long-term protection after vaccination.

Traveler's Diarrhea.

Travelers' diarrhea (TD) is the most important health issue among international travelers. In high risk areas, 50-90% of travelers may experience an episode of TD. The risk of acquiring TD is influenced by factors such as the destination, duration of stay, standard of accommodation, type of travel, age of the traveler, and also by individual risk factors. Most cases of TD are caused by bacteria; treatment for TD are loperamide and antibiotics. Preventive strategies such as hygiene measures have limited impact. Prophylactic intake of antibiotics or vaccines to prevent from TD can be considered in special situations.