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.

[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.

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.

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

[Travel vaccination recommendations for Central and Eastern European countries based on country-specific risk profiles]. / Länderspezifische Risikoprofile als Basis für reisemedizinische Impfprävention in Mittel-, Ost- und Südosteuropa.

Within the last years, an increasing trend of voyages to Central and Eastern European destinations could be observed. However, Europeans travelling within their own continent do not consider themselves as travellers exposed to possibly travel-associated infections since problem awareness among tourists as well as consulting doctors is rather scanty. The objective of this expert statement is to outline country-specific risk profiles as well as guidelines with regard to relevant travel immunizations for this region. These recommendations are mainly based on risk estimates according to national incidences and prevalences of vaccine-preventable diseases such as hepatitis A, hepatitis B, typhoid fever, meningococcal meningitis, rabies, and tick-borne encephalitis.

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.

Drug prophylaxis for travelers' diarrhea.

Travelers' diarrhea is the most common health impairment in persons visiting developing countries, affecting 20% to >50% of tourists. Although it is usually benign, travelers' diarrhea represents a considerable socioeconomic burden for both the traveler and the host country. The most common enteropathogens are enterotoxigenic and enteroaggregative Escherichia coli. Travelers' compliance with dietary precautionary measures is poor. Despite the excellent protection rates provided by antibiotics, routine administration of prophylaxis is currently not recommended because of potential adverse reactions. Of the various antibiotics that have been tested, quinolones are considered to be the first choice worldwide; however, quinolone-resistant pathogens are increasingly being isolated. Because it is frequently administered and provides only moderate protection, bismuth subsalicylate is not considered a recommendable option for prophylaxis in Europe, where it is rarely available anyhow. To date, no probiotic has been able to demonstrate clinically relevant protection worldwide. In conclusion, there is no satisfactory prophylactic option, and worldwide monitoring of antimicrobial susceptibility patterns and the search for novel antimicrobial agents, such as nonabsorbed antibiotics, and nonantibiotic medications should continue.

A randomized, open-label study of the immunogenicity and reactogenicity of three lots of a combined typhoid fever/hepatitis A vaccine in healthy adults.

BACKGROUND: Travelers are often advised to receive both the typhoid fever and hepatitis A virus (HAV) vaccines, particularly when going to areas where the 2 diseases are endemic. Thus, combined administration of these vaccines could make immunization more acceptable by reducing the number of injections needed. OBJECTIVE: This study compared the safety profiles and immunogenicity of 3 batches of a combined typhoid fever/HAV vaccine administered using a dual-chamber bypass syringe. METHODS: This randomized, open-label study was conducted at 2 university-based travel clinics in Germany and Austria. Subjects received a single IM injection from 1 of 3 batches of the combined vaccine. Blood samples were drawn immediately before and 28 days after vaccination to evaluate the response to the 2 antigens by assessing geometric mean titers (GMTs) and rates of seroconversion and seroprotection. Subjects recorded all adverse events (AEs) occurring during the study period in a diary. RESULTS: Six hundred ten healthy adults were enrolled in the study. Twenty-eight days after vaccination, 90.6% of the study population had protective typhoid Vi antibody titers (> or = 1 microg/mL) and 100% had protective HAV antibody titers (> or = 20 mIU/mL). Seroconversion rates and GMTs were not significantly different between the 3 batches. There were no differences with regard to local or systemic AEs between the 3 batches of vaccine. There were no immediate adverse reactions (within 30 minutes of vaccination) and no serious AEs related to vaccination. Of 609 evaluable subjects (1 was lost to follow-up after the first visit), 555 (91.1%) experienced > or = 1 local reaction within the first 7 days after vaccination, mainly pain at the injection site (550 [90.3%]), but only 26 (4.3%) described this pain as severe. Vaccine-related headache and mild to moderate asthenia were each reported by 54 subjects (8.9%). Symptoms resolved spontaneously in all cases. CONCLUSIONS: The 3 batches of the combined typhoid fever/HAV vaccine administered by dual-chamber bypass syringe were equally well tolerated and effective in healthy adults, and did not differ significantly in terms of GMTs or seroconversion rates.

Unexpected frequency, duration and spectrum of adverse events after therapeutic dose of mefloquine in healthy adults.

The frequency and spectrum of adverse events associated with the antimalarial therapeutic regimen of mefloquine (MQ) (750 and 500 mg at an interval of 6 h) was assessed in 22 healthy volunteers who were monitored for 21 days following drug administration. An unexpected high frequency of side effects of any grade were reported by all 22 subjects. The most commonly reported symptoms were vertigo (96%), followed by nausea (82%) and headache (73%). Participants suffering from severe (grade 3) vertigo (73%) required bed rest and specific medication for 1 to 4 days. More females than males reported severe adverse reactions. The majority (77.3%) of the participants (f: 8/12, m: 9/10) showed symptom resolution within 3 weeks (510 h) after drug administration. Biochemical and haematological findings stayed within the normal range of values, but showed nevertheless a significant rise of Na, Cl, Ca, bilirubin, GGT and LDH. The unexpectedly high frequency and severity of adverse reactions after normal therapeutic dosage of MQ in healthy subjects may influence future recommendations regarding the use of MQ for stand-by treatment of suspected malaria in travellers.

[Immunization recommendations for travel in the Mediterranean area]. / Reisemedizinische Impfempfehlungen für den Mittelmeerraum.

The Mediterranean region is a popular destination for tourists during the summer. However, European tourists, who are travelers within their own continent, do not consider themselves exposed to possible, travel-associated infections, since problem awareness among tourists as well as doctors is rather weak. The objective of this consensus paper is to outline guidelines with regard to relevant travel immunizations for Mediterranean destinations. These recommendations are mainly based on risk calculations according to country-specific incidences and prevalences of vaccine-preventable diseases such as hepatitis A, hepatitis B, typhoid fever, meningococcal meningitis, rabies, and tick-borne encephalitis.

New vaccination strategies for low- and non-responders to hepatitis B vaccine.

The currently available recombinant hepatitis B vaccines are safe, efficacious and immunogenic. Nevertheless, a high rate of low- and nonresponsiveness to the current vaccine poses a problem since this group remains susceptible to infection with hepatitis B virus. Efforts are underway to develop new vaccines and strategies to enhance seroprotection rates. One possibility under investigation is the low-dose intradermal administration of vaccine since the immune system is well represented in both the epidermis and the dermis. Despite encouraging results concerning the immunogenicity in previous non-responders, the main difficulty is the technique of administration and unacceptable local adverse effects. Promising data have emerged from clinical trials evaluating the immunogenicity of new recombinant vaccines containing the complete pre-S1 and pre-S2 regions of HbsAg and, more recently, of novel adjuvanted hepatitis B vaccines. Future approaches include DNA vaccination and expression of HbsAg determinants in live recombinant vectors.

[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.

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.

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.

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.

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.

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.