Occurrence and identification of risk areas of Ixodes ricinus-borne pathogens: a cost-effectiveness analysis in north-eastern Italy

<p>Abstract</p> <p>Background</p> <p><it>Ixodes ricinus</it>, a competent vector of several pathogens, is the tick species most frequently reported to bite humans in Europe. The majority of human cases of Lyme borreliosis (LB) and tick-borne encephalitis (TBE) occur in the north-eastern region of Italy. The aims of this study were to detect the occurrence of endemic and emergent pathogens in north-eastern Italy using adult tick screening, and to identify areas at risk of pathogen transmission. Based on our results, different strategies for tick collection and pathogen screening and their relative costs were evaluated and discussed.</p> <p>Methods</p> <p>From 2006 to 2008 adult ticks were collected in 31 sites and molecularly screened for the detection of pathogens previously reported in the same area (i.e., LB agents, TBE virus, <it>Anaplasma phagocytophilum, Rickettsia </it>spp., <it>Babesia </it>spp., "<it>Candidatus Neoehrlichia mikurensis</it>"). Based on the results of this survey, three sampling strategies were evaluated <it>a</it>-<it>posteriori</it>, and the impact of each strategy on the final results and the overall cost reductions were analyzed. The strategies were as follows: tick collection throughout the year and testing of female ticks only (strategy A); collection from April to June and testing of all adult ticks (strategy B); collection from April to June and testing of female ticks only (strategy C).</p> <p>Results</p> <p>Eleven pathogens were detected in 77 out of 193 ticks collected in 14 sites. The most common microorganisms detected were <it>Borrelia burgdorferi </it>sensu lato (17.6%), <it>Rickettsia helvetica </it>(13.1%), and "<it>Ca. N. mikurensis</it>" (10.5%). Within the <it>B. burgdorferi </it>complex, four genotypes (i.e., <it>B. valaisiana, B. garinii, B. afzelii</it>, and <it>B. burgdorferi </it>sensu stricto) were found. Less prevalent pathogens included <it>R. monacensis </it>(3.7%), TBE virus (2.1%), <it>A. phagocytophilum </it>(1.5%), <it>Bartonella </it>spp. (1%), and <it>Babesia </it>EU1 (0.5%). Co-infections by more than one pathogen were diagnosed in 22% of infected ticks. The prevalences of infection assessed using the three alternative strategies were in accordance with the initial results, with 13, 11, and 10 out of 14 sites showing occurrence of at least one pathogen, respectively. The strategies A, B, and C proposed herein would allow to reduce the original costs of sampling and laboratory analyses by one third, half, and two thirds, respectively. Strategy B was demonstrated to represent the most cost-effective choice, offering a substantial reduction of costs, as well as reliable results.</p> <p>Conclusions</p> <p>Monitoring of tick-borne diseases is expensive, particularly in areas where several zoonotic pathogens co-occur. Cost-effectiveness studies can support the choice of the best monitoring strategy, which should take into account the ecology of the area under investigation, as well as the available budget.</p

Synthesis and Electrophilic Substitution of Pyrido[2,3,4-kl]acridines

Abstract: Several new pyrido[2,3,4-kl]acridines were synthesized by reacting naphthoquinone, juglone or cyclohexan-1,3-dione with β,β’-diaminoketones in a biomimetic reaction. The structure of all new compounds was elucidated by NMR and MS spectroscopy. Electrophilic substitution, mainly nitration, of the various compounds was undertaken and the substitution positions determined. A series of derivatives was prepared and their cytotoxicity towards P-388 mouse lymphoma cells analysed. The most cytotoxic derivatives were found to have IC50’s of 0.05 and 0.1 ug/ml