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.

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

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.

Hospital-based active surveillance of childhood pertussis in Austria from 1996 to 2003: estimates of incidence and vaccine effectiveness of whole-cell and acellular vaccine.

BACKGROUND: This study was undertaken to analyse the epidemiology of pertussis disease among hospitalised children during the transition period from whole-cell to acellular pertussis vaccine in order to compare the respective estimates of vaccine effectiveness. METHODS: Surveillance was conducted between 1 January 1996 and 31 December 2003. The data originated from a voluntary hospital-based surveillance network including all 44 nationwide paediatric departments. RESULTS: The mean annual hospitalisation incidence for children decreased over time, from 27.9 per 100,000 population in 1996 to 6.8 cases per 100,000 population in 2003. The mean age of reported hospitalised pertussis cases was 4.7 years (+/- 5.5 S.D.), increasing from 4.06 years (+/- 4.6 S.D.) in 1996 to 5.5 years (+/- 8.6 S.D.) in 2003. Estimated vaccine effectiveness (after three vaccine doses) was 79% for the whole-cell versus 92% for the acellular pertussis vaccine. A significantly higher proportion (19%) of fully immunised children among hospitalised patients was observed for the years where only acellular pertussis vaccine was used compared to whole-cell vaccine era (2%) which was, however, mainly due to children above 2 years of age. CONCLUSIONS: Our results imply that despite high vaccination coverage rate, pertussis is still a considerable cause of hospital admissions in children in Austria where it remains to be shown that the novel vaccination strategy of additional booster doses in adolescents and adults will control disease in the long term.

Prospective surveillance of incidence, serotypes and antimicrobial susceptibility of invasive Streptococcus pneumoniae among hospitalized children in Austria.

OBJECTIVES: This study was undertaken to analyse incidence rates, serotype distribution and antimicrobial resistance patterns of invasive Streptococcus pneumoniae isolates from hospitalized children up to 5 years of age with invasive pneumococcal disease (IPD), including meningitis, in Austria. METHODS: From February 2001-January 2003, nationwide prospective surveillance was conducted that included all paediatric hospitals and clinical microbiological laboratories. All invasive pneumococci isolated were serotyped and tested for antimicrobial susceptibility. RESULTS: The mean annual incidence rates of IPD per 10 000 population for the age groups <24 months and <60 months were 14.5 (7.7 for meningitis) and 13.7 (6.0 for meningitis), respectively. The case fatality rate was 6% for IPD and 12% for meningitis. Of all IPD cases, 69.6% (73.1% for meningitis) were covered by serotypes and 83.9% (88.5% for meningitis) by cross-protection of vaccine-related serotypes. Intermediate penicillin G susceptibility (MIC 0.12-1 mg/L) was found in 12/56 strains. No penicillin G-resistant strains were found. A total of 19/56 isolates showed decreased susceptibility to macrolide agents (MIC >/= 1 mg/L). CONCLUSIONS: The IPD incidence rate was similar, and serotype coverage of the 7-valent conjugated vaccine marginally superior, to Germany. The surprisingly high level of antimicrobial resistance among invasive isolates considerably amplifies the potential impact of a childhood pneumococcal vaccination programme in Austria.