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.

[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.

Persistence of antibodies in 4-8 year old Austrian children after vaccination with hexavalent DTaP-HBV-IPV/Hib and MMR vaccines.

To determine the proficiency of the Austrian childhood vaccination schedule to induce long lasting seroprotection against vaccine preventable diseases a seroepidemiological study in 348 children between four and eight years of age was conducted. Antibodies against diphtheria, tetanus, pertussis, hepatitis B, measles, mumps and rubella antigens were assessed in children, who had been vaccinated with hexavalent DTaP-HBV-IPV/Hib vaccines at three, four, five months and in the second year of life and/or MMR vaccines in the second year of life at least once, but mostly twice. High seroprotection rates (SPRs) were detected for tetanus (96%) and measles (90%). SPRs regarding diphtheria and mumps were 81% and 72%, respectively. Rubella-SPRs were 68% in females and 58% in males. Hepatitis B-antibody levels ≥10 mIU/mL were present in 52%; antibodies against pertussis were detected in 27% of the children. SPRs for measles and rubella depended on the interval since last vaccination; mumps-antibodies were significantly lower after one MMR-vaccination only. Antibodies against diphtheria, tetanus and pertussis depended on the interval since last vaccination while HBs-antibodies did not. The low levels of antibodies 1-7 years after vaccination against pertussis, rubella and mumps after only one vaccination should be considered when recommending new vaccination schedules.

Herd immunity after two years of the universal mass vaccination program against rotavirus gastroenteritis in Austria.

Austria was the first country in Europe implementing a universal mass vaccination program against rotavirus gastroenteritis (RV-GE) for all infants nationwide. Epidemiological data from a hospital based surveillance system show that incidence rates of children hospitalized with RV-GE decreased in 2009 compared to 2008 and compared to the prevaccination period 2001-2005. Decreasing hospitalization-rates from RV-GE were observed in children of all age groups, even in those not eligible for vaccination according to their age, suggesting herd immunity induced by universal mass vaccination against RV-GE. In 2009 the disease burden was highest in children below three months of age stressing the importance of the early start of the immunization course.

The seroepidemiology of Bordetella pertussis in Israel--Estimate of incidence of infection.

This study was undertaken to estimate the magnitude of Bordetella pertussis infections in a highly vaccinated population in Israel in order to evaluate the relationship between clinical notification data and serology-based evidence of infection. A cross-sectional survey was conducted on a total of 1982 serum samples from the National Serum Bank, collected from January 2000 through December 2001, in order to monitor high levels of pertussis toxin (PT) IgG antibody indicative of recent B. pertussis infection, by standardized methods. The estimation yielded an infection incidence rate of 2448 per 100,000 population (> or =3 years of age) for the year 2000 compared to an annual incidence of reported pertussis of 5.6 per 100,000 for the same period. The peaks of estimated incidence of infection were found in the groups of 15-19-year olds (5245 per 100,000) and older than 60 years (6469 per 100,000), whereas the majority of clinical pertussis cases were reported for the 10-14-year olds (20.5 per 100,000). The findings clearly show that despite a high vaccination coverage rate (>93%), there is still a considerable circulation of B. pertussis, particularly in adolescents and elderly. Population-based serosurveillance for pertussis offers the potential to assist interpretation of trends independent of notification and diagnostic bias.

[The profile of Israeli travelers to developing countries: perspectives of a travel clinic].

BACKGROUND: The number of Israeli travelers is increasing, including the number of travelers to developing countries. AIM: This study aimed to characterize the profile of Israeli travelers to developing countries. METHODS: Data regarding demographics, travel destinations, trip duration and the purpose of travel were collected on travelers attending the pre-travel clinic at the Sheba Medical Center during a period of 9 years. RESULTS: Between the dates 1/1/1999 and 31/12/2007, 42,771 travelers presented for consultation at the Sheba Medical Center pre-travel clinic. The average age was 30.8 +/- 13.4 years and 54% of the travelers were males. The female proportion increased from 42% in 1999 to 49% in 2006. There was a steady increase in the number of travelers attending our clinic, except in 2003 (coinciding with the SARS epidemic). Post-army backpackers (20-25 year-old age group) were only 43% of the travelers. Children (<18 years), and elderly (>60 years) comprised 4.4% and 4.6% of the travelers, respectively. The favorite destinations were Asia (55%), followed by Latin America (27%) and Africa (13%). The distribution of travel destinations varied significantly during the study period. Of note is the sharp decline in travel to Africa following the terrorist attack in Mombassa, Kenya (November 2002). The median trip duration changed during the study period, from 30 to 45 days, between 1999-2004 and 2005-2007 respectively. The majority (87%) of voyagers traveled for pleasure, 6% went for business, and 7% were representatives of governmental organizations. CONCLUSION: This study found an increasing diversity in the traveler population (more women, more children and older travelers) and more diversity in travel destinations. Disease outbreaks and terrorist attacks had transient negative impacts on the number of travelers.

Universal mass vaccination against rotavirus gastroenteritis: impact on hospitalization rates in austrian children.

BACKGROUND: Since July 2007, rotavirus vaccinations have been subsidized in Austria for all children from the seventh week up to the sixth month of life. Vaccination coverage over the whole period was 72% with an increase to 87% in 2008. METHODS: In a sentinel network including 11 pediatric hospital wards in Austria, data of children up to 15 years of age and hospitalized due to rotavirus gastroenteritis between January 2001 and December 2008 have been collected. RESULTS: The hospitalization rates of children up to 12 months of age with rotavirus gastroenteritis were 2066 x 10(-5) between 2001 and 2006 and decreased to 631 x 10(-5) in 2008. For children between 12 and 24 months of age the hospitalization rate decreased from 1822 x 10(-5) (2001-2006) to 1456 x 10(-5) in 2008. In children aged 2 to less than 5 years, incidence rates were 436 x10(-5) (2001-2006) and 461 x 10(-5) in 2008. In older children, the hospitalization rates remained unchanged. In the target population for the RV-vaccine, a decrease of hospitalization rates due to rotavirus gastroenteritis of 74% was observed compared to the era before the introduction of the vaccine. The field effectiveness of the vaccine was estimated between 61% and 98%, depending on assumptions about the vaccination status. CONCLUSIONS: Within 18 months, the universal mass vaccination program against rotavirus led to a substantial decrease in the hospitalization rates of the target cohort of the immunization program in Austria.

Booster vaccinations against tick-borne encephalitis: 6 years follow-up indicates long-term protection.

Five and 6 years post-booster, immunity to tick-borne encephalitis (TBE) virus was assessed in 225 and 195 vaccinees, respectively, out of 430 healthy volunteers with at least three TBE-immunizations prior to study inclusion and booster intervals exceeding recommended limits. Neutralizing antibody titers of > or = 1:10 (reliable level of protection) were present in 86-96% depending on age group, with lower percentages in participants >60 years. TBE antibody levels remained stable for many years in most vaccinees. However, in a few persons a shorter period of protection against TBE was indicated. Therefore, recommendations on booster intervals in TBE endemic areas should be adapted by weighting the risk of infection against the risk of short-lived immunity.

Correlation between humoral and cellular immune responses and the expression of the hepatitis A receptor HAVcr-1 on T cells after hepatitis A re-vaccination in high and low-responder vaccinees.

INTRODUCTION: We recently published a study on the persistence of seroprotection 10 years after primary hepatitis A vaccination in an unselected study population of 1014 vaccinees. The majority of these vaccinees still exhibited sufficient protective antibody levels, while 2% displayed antibody concentrations below detection level. In order to investigate whether the low antibody levels were due to decline after primary vaccination or due to an intrinsic inability to sufficiently respond to hepatitis A antigen, we sought to recruit these low/no responder vaccinees to characterize their immune responses in more detail after booster vaccination in comparison to high responder vaccinees. MATERIALS AND METHODS: Prior to and one week after booster vaccination with a hepatitis A vaccine, antibody levels, cytokine levels (IL-2, IFN-gamma and IL-10) and CD surface marker expression on peripheral blood mononuclear cells were determined in a study population comprised of 52 individuals. Additionally, the hepatitis A HAV cellular receptor 1 (HAVcr-1) TIM-1, being also expressed on CD4+ T cells and associated with immunomodulatory properties, was measured by RT-PCR before and after hepatitis A booster. RESULTS: Our data indicate that there is indeed a small group of hepatitis A vaccinees that can be classified as low/no responders as their antibody levels remain below the seroprotection level of 20mIU/ml after booster vaccination. We further describe a good correlation between antibody concentrations and cellular responses, showing that low antibody production is associated with low antigen specific cytokine levels (IL-2, IFN-gamma, IL-10) and vice versa. While there was no significant difference in the expression of the most common surface markers on T and B cells before and after booster vaccination in low and high responder vaccinees, the expression of HAVcr-1 on CD4 T cells correlated significantly with the antibody responses and cytokine levels, suggesting this receptor as cellular prediction marker of immune responsiveness to hepatitis A. CONCLUSION: Whether hepatitis A low/non-responders deserve particular attention as a risk group or might display certain resistance to hepatitis A infection due to a lack of the hepatitis A receptor needs further investigations. At this stage we suggest that persons at high exposure risk should be carefully observed.

Pretravel consultation: rapid dipstick test as a decision guidance for the application of tetanus booster vaccinations.

BACKGROUND: When deciding whether to administer a tetanus vaccination--for international travel or injury--a subject's vaccination certificate should be investigated. As many people lack valid vaccination cards and are unable to recall their vaccination history, the Tetanos Quick Stick (TQS) test rapidly detects protective tetanus immunoglobulin IgG antibodies in whole blood, serum, or plasma. This immunochromatographic dipstick test yields a positive or negative result. METHODS: Our study evaluates the effectiveness of the TQS test by comparing the binary TQS test results of 100 sera with the tetanus antibody levels as measured by the standardized enzyme-linked immunosorbent assay (ELISA) method. We used the TQS test to determine whether a person needed a tetanus booster vaccination. If the test showed a clearly visible line that was similar to the control line, the result was determined to be positive. RESULTS: All positive TQS test results had a concentration of IgG antibodies above 0.5 IU/mL as measured by ELISA, indicating that no booster vaccination was required. Similarly, in all cases with an antibody level below 0.1 IU/mL, where a vaccination would have been recommended based on the ELISA test result, the TQS test yielded a negative result. The positive predictive value and the specificity for the dipstick test were therefore 100%. CONCLUSIONS: The TQS test is a reliable, fast, and cost-effective means of identifying subjects with a preexisiting level of tetanus IgG antibodies above approximately 0.5 IU/mL. This can help to avoid unnecessary tetanus vaccinations in travel clinics, emergency departments, and practices of family doctors.

Effect of pre-existing anti-tick-borne encephalitis virus immunity on neutralising antibody response to the Vero cell-derived, inactivated Japanese encephalitis virus vaccine candidate IC51.

Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in Asia with a case fatality rate up to 35% and long-term sequelae up to 75%. This active-controlled, randomized, multi-centre, observer-blind, phase III trial investigated the neutralising antibody response to the new Japanese encephalitis (JE) vaccine IC51 in subjects with (N=81) and without (N=339) pre-existing tick-borne encephalitis (TBE) vaccine induced antibodies as determined by TBE enzyme-linked immunosorbent assay IgG (ELISA). Neutralising antibody response was statistically superior in TBE ELISA-positive subjects compared to TBE ELISA-negative subjects after the first (p<0.0001) but not after the second vaccination with IC51. Thus, pre-existing vaccine-induced TBE immunity enhances the neutralising JEV-specific antibody response after a single IC51 vaccination.

Advances in vaccination against tick-borne encephalitis.

Tick-borne encephalitis (TBE) poses a growing health problem in many European countries and parts of Northern Asia. Thus, vaccination has been employed successfully for many years in endemic countries. Long-term experience gained from widespread use, however, prompted the development of improved vaccine formulations of the two licensed European TBE vaccines. Moreover, recent clinical trials also suggested the maintenance of high values of postvaccination neutralizing TBE antibodies for a longer period than expected; thus, also resulting in modifications with regards to immunization regimens. Recent advances in recombinant DNA technology have opened up future opportunities for developing novel live-attenuated vaccines against TBE virus and other flaviviruses. Animal experiments demonstrated safety and high immunogenicity profiles for these mutants; thus, making them promising vaccine candidates that will need to demonstrate a clear advantage if they are going to be alternatives to the traditional vaccines. Systematic TBE case monitoring by raising problem awareness, both inside and outside endemic regions, appears essential to provide evidence for a widely accepted TBE travel-vaccination recommendation in the future.

Impact of a pertussis booster vaccination program in adolescents and adults on the epidemiology of pertussis in Austria.

BACKGROUND: A resurgence of pertussis has been observed in several countries; however, inconsistent data are available for Europe. In Austria, routine pertussis vaccination for babies is administered at 3, 4, and 5 months, and in the second year of life. Since 2002, regular boosters for all persons >6 years of age (including adults) are recommended. This study was undertaken to analyze epidemiologic trends of laboratory-reported pertussis to evaluate current vaccination strategy in Austria. METHODS: Epidemiologic surveillance of laboratory-reported pertussis was conducted from January 1, 2000, to December 31, 2005. Infection was confirmed by positive serology, by positive culture of Bordetella pertussis, or by detection of sequences of the pertussis toxin gene by real-time polymerase chain reaction (RT-PCR). Data were assessed by age, hospitalization rate, seasonality, and incidence rate. RESULTS: During the observation period 4395 reported cases of pertussis were eligible for analysis. The mean annual incidence increased from 6.4 per 100,000 population in 2000 to 11.1 cases per 100,000 population in 2005. Incidence rates were highest among children less than 1 year of age. Decreasing rates were observed for children and adolescents <16 years of age, whereas increasing rates were detected for persons 16 years of age and older. The mean age of reported pertussis cases increased from 30 years (+/-25.9 SD) in 2000 to approximately 44 years (+/-23.7 SD) in 2005. Hospitalization rates were highest in infants <6 months (86%) and lowest in those 10 to <50 years of age (17%), followed by an increase to 80% in persons 85 years of age and older. In general, no seasonal occurrence of disease was apparent. CONCLUSIONS: Pertussis incidence remains high among adults implying that coverage rates regarding booster vaccinations for adolescents and adults still are too low. Reinforced application of the current booster strategy is needed.

Epidemiology of travel-associated and autochthonous hepatitis A in Austrian children, 1998 to 2005.

BACKGROUND: In Austria, being an area of low hepatitis A endemicity, every year, several cases of this infectious disease are reported. The aim of the present study was to provide data on disease and hospitalization of children below the age of 15 for imported and autochthonous hepatitis A in Austria. METHODS: Nationwide, active, hospital-based surveillance during the period 1998 to 2005. RESULTS: During this 8-year observation period, 413 children below 15 years of age were hospitalized with acute hepatitis due to infection with hepatitis A . The mean annual incidence of hospitalization per 100,000 population was 3.8, with a decreasing trend from 1998 to 2005. The mean length of hospital stay attributable to hepatitis A was 6.5 days. The mean annual number of days of hospitalization attributable to acute hepatitis A infection in children below 15 years of age was 335 days. Information on origin of infection was available in 48% of the reports, the majority of which (69%) were in consequence of infection import. The mean annual incidence of travel-associated, hospitalized hepatitis A cases was 1.3 per 100,000, showing a lesser decrease rate over the observation period than the total hospitalization incidence. CONCLUSIONS: In an area of low hepatitis A endemicity such as Austria, hospitalization incidence of children is still at a considerable level. Our findings contribute to an open discussion about universal childhood vaccination.

Antibody persistence following booster vaccination against tick-borne encephalitis: 3-year post-booster follow-up.

In order to evaluate the long-term immunity 2 and 3 years after booster vaccination against tick-borne encephalitis (TBE) following time intervals 3 years and longer since last TBE immunization, 195 (mean age 50.5+/-15.1 years) and 240 subjects (mean age 47.0+/-15.4 years), respectively, who had received a single booster dose in a preceding study, returned for a serological follow-up. Antibody concentrations were measured by neutralization test (NT) and ELISA. Protective TBE antibody levels (NT>or=10) were noted in 96% (187/195) of the subjects at year 2 and 97% (232/240) at year 3 post-booster. At both years, GMTs (NT) of all age groups were above detection limit (>or=2), showing GMT-NT of 54.5 (95% CI: 47.7-62.4) and 69.1 (95% CI: 60.7-78.6), respectively. GMTs were significantly lower in vaccinees>or=50 years of age (p<0.001 for both years). Comparison of GMTs at years 2 and 3 post-booster vaccination with pre-booster values revealed similar antibody titers at all three reading points. Besides an expected rapid decline of TBE antibodies shortly after booster administration, the kinetic curve also suggested maintenance of high values of neutralizing TBE antibodies for a period longer than expected, thus confirming the recent recommendations regarding the extension of TBE booster intervals.

Persistence of seroprotection 10 years after primary hepatitis A vaccination in an unselected study population.

Hepatitis A vaccines have been demonstrated to be highly immunogenic. Mathematical models have predicted antibodies to persist for at least 20-25 years. Most of these studies have been conducted in young and healthy study populations. We aimed to evaluate long-term immunity 10 years following complete primary immunization according to a 3-dose schedule (Havrix 720 El.U at months 0, 1, 6-12) in an adult and unselected study population. In total, 999 (98.3%) of 1016 vaccinees (mean age 54.7+/-S.D. 13.0), tested 10 years after primary vaccination, still had protective antibody levels (> or = 10 mIU/ml) as measured by ELISA. An anti-HAV titer cut off level of 11,400 mIU/ml was calculated to differentiate between vaccine-induced and infection-induced titer levels. The vaccine-induced geometric mean titer (GMT) was 406.1 mIU/ml (95% CI: 369.2-446.7 mIU/ml), showing an age-related trend, the 10-years seroprotection rate (SPR) was 97.9%. Females exhibited significantly higher GMTs than male vaccinees (p<0.001). The only parameter predicting a titer below 10 mIU/ml 10 years after vaccination was the body mass index (p=0.001). This study confirms that protection following primary hepatitis A vaccination persists for more than 10 years.

Active hospital-based surveillance of rotavirus diarrhea in Austrian children, period 1997 to 2003.

BACKGROUND: Rotavirus is the most common pathogen causing severe dehydrating diarrhea in infants and young children worldwide. Any decision on implementation of rotavirus vaccination will be strongly influenced by the expected reduction in severe and therefore costly outcomes associated with rotavirus infection. The aim of this study was to provide data on hospitalization of young children with rotavirus infection in Austria. METHODS: The data were derived from active hospital-based sentinel surveillance for rotavirus during the period 1997 to 2003. RESULTS: During this period 25,600 children<15 years of age were hospitalized with acute laboratory-confirmed rotavirus gastroenteritis, the infection showing seasonal peaks between February and March. In 5 % of the cases first symptoms of diarrhea occurred at a minimum of 48 hours after hospital admission, indicating healthcare-associated origin of infection. The mean annual incidence of hospitalization per 100,000 population for the age group<5 years was 766 and for those<2 years 1742, the latter meaning that 1 in 60 Austrian children up to 2 years of age required hospitalization. An average peak incidence was observed between 8 and 14 months of age, with an average of 68% of the reported cases occurring in children aged