Topical azithromycin for the prevention of Lyme borreliosis: a randomised, placebo-controlled, phase 3 efficacy trial.

BACKGROUND: Lyme borreliosis develops in 1-5% of individuals bitten by ticks, but with a diagnostic gap affecting up to 30% of patients, a broadly applicable pharmacological prevention strategy is needed. Topical azithromycin effectively eradicated Borrelia burgdorferi sensu lato from the skin in preclinical studies. We assessed its efficacy in human beings. METHODS: In this randomised, double-blind, placebo-controlled, multicentre trial done in 28 study sites in Germany and Austria, adults were equally assigned to receive topical 10% azithromycin or placebo twice daily for 3 consecutive days, within 72 h of a tick bite being confirmed. Randomisation numbers, which were stratified by study site, were accessed in study centres via an interactive voice-response system, by pharmacists not involved in the study. The primary outcome was the number of treatment failures, defined as erythema migrans, seroconversion, or both, in participants who were seronegative at baseline, had no further tick bites during the study, and had serology results available at 8 weeks (intention-to-treat [ITT] population). This study is registered with EudraCT, number 2011-000117-39. FINDINGS: Between July 7, 2011, and Dec 3, 2012, 1371 participants were randomly assigned to treatment, of whom 995 were included in the ITT population. The trial was stopped early because an improvement in the primary endpoint in the group receiving azithromycin was not reached. At 8 weeks, 11 (2%) of 505 in the azithromycin group and 11 (2%) of 490 in the placebo group had treatment failure (odds ratio 0·97, 95% CI 0·42-2·26, p=0·47). Topical azithromycin was well tolerated. Similar numbers of patients had adverse events in the two groups (175 [26%] of 505 vs 177 [26%] of 490, p=0·87), and most adverse events were mild. INTERPRETATION: Topical azithromycin was well tolerated and had a good safety profile. Inclusion of asymptomatic seroconversion into the primary efficacy analysis led to no prevention effect with topical azithromycin. Adequately powered studies assessing only erythema migrans should be considered. A subgroup analysis in this study suggested that topical azithromycin reduces erythema migrans after bites of infected ticks. FUNDING: Ixodes AG.

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.

Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models.

Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1-6 and determined the infectivity titer of acute-phase plasma pools in additional animals. The courses of first- and second-passage infections were similar, with early appearance of viremia, HCV RNA titers of >10(4.7) IU/mL, and development of acute hepatitis; the chronicity rate was 56%. The challenge pools had titers of 10(3)-10(5) chimpanzee infectious doses/mL. Human liver-chimeric mice developed high-titer infections after inoculation with the challenge viruses of genotypes 1-6. Inoculation studies with different doses of the genotype 1b pool suggested that a relatively high virus dose is required to consistently infect chimeric mice. The challenge pools represent a unique resource for studies of HCV molecular virology and for studies of pathogenesis, protective immunity, and vaccine efficacy in vivo.

[Medical clearance for missions abroad (EEU): definitions, recommendations for use and performance]. / Entsendungseignungsuntersuchung (EEU): Definition, Empfehlungen zum Untersuchungsaufwand und Einsatz.

Standards for medical clearance for private or business missions abroad are--at least in the German speaking countries--not clearly defined and mostly derived from the old terminus "Tropentauglichkeit" which means fit for mission in the tropics. The authors now define a new standard, called "Entsendungstauglichkeitsuntersuchung" which means clearance of fitness for all types of missions abroad, independent of distinct climatic zones. To meet the inhomogenous requirements of different institutions and different types of missions the medical examination proposed follows a modular structure to optimize economic and medical use of resources. Moreover, as Austria, Germany and Switzerland have different legal and economic postulates, the medical examination has to be adapted to the different premises. The definition and description of this special type of "medical clearance for missions abroad" is supplemented by recommendations for definitions of clients who should undergo such an investigation and the professionals who should perform this type of investigation. Additionally, results of this type of medical clearance are defined and prophylactic aspects in terms of pre-travel advice are mentioned.

A controlled trial of tick-borne encephalitis vaccination in patients with multiple sclerosis.

The aim of this study was to investigate a possible link between a single vaccination against tick-borne encephalitis (TBE) and the appearance of one or more new cerebral lesions in magnetic resonance imaging (MRI) and/or a clinical relapse of MS. Fifteen MS patients with documented history of MS relapses living in a TBE endemic area were matched with 15 patients selected from a patient database containing 500 cases of MS. Three patients in each group were unvaccinated while all others had basic immunisation and regular booster vaccinations. Patients of the vaccination group received a single dose (3.3 microg) of a TBE vaccine. TBE antibodies were detected by ELISA and confirmed by neutralisation test. MRI was used as marker for disease activity and progression in addition to the clinical neurological examination. No association was seen between TBE vaccination and MRI detected disease activity, clinical relapse or disease progression of MS.