Project description:Effective preventive strategies are available to control Echinococcus multilocularis in foxes in order to reduce the human infection risk. Reduction of E. multilocularis prevalence in foxes was achieved in various studies by distributing praziquantel-containing bait by hand or by aircraft in either rural or settlement areas. Here, an integrated approach is described from southern Germany (district of Starnberg). Baseline data were obtained in winter 2002/03, when the prevalence rate in the project area was 51%. Between December 2005 and December 2011, air distribution of bait in agricultural and recreational areas was combined with distribution by hand in towns and villages, in order to cover the entire fox population, with a bait density of 50 pieces / km2 (baiting area: 213 km2). In addition, a control area without anthelmintic treatment was selected. Prevalence was reduced in the baiting area to 1% by March 2007. Subsequently, from 2007 to the end of 2011, prevalence rates remained at a low level with 2.4% (2007), 2.4% (2008), 2.6% (2009), 1.2% (2010) and 0.0% (2011). In the un-baited control area the prevalence rates remained high, ranging from 19.6% to 35.1% with an average of 27.3%. During the 6 years of anthelmintic treatment, differences between baiting and control areas were highly significant (P<0.001). In the suburban and urban parts of the study area prevalence could be reduced to less than 1%, i.e. to a level below the limit of detection, which was maintained even after the measures had been discontinued. The applicability and effectiveness of anthelmintic baiting was therefore confirmed even for a heavily settled and fragmented landscape, which posed challenges for practical application of the control measures. The cost of the project ranged between € 1.70 and € 2.00 per inhabitant of the baiting area per year.
Project description:BackgroundAlveolar echinococcosis (AE), caused by the metacestode larval stage of the fox-tapeworm Echinococcus multilocularis, is a chronic zoonosis associated with significant modulation of the host immune response. A role of regulatory T-cells (Treg) in generating an immunosuppressive environment around the metacestode during chronic disease has been reported, but the molecular mechanisms of Treg induction by E. multilocularis, particularly parasite immunoregulatory factors involved, remain elusive so far.Methodology/principal findingsWe herein demonstrate that excretory/secretory (E/S) products of the E. multilocularis metacestode promote the formation of Foxp3+ Treg from CD4+ T-cells in vitro in a TGF-β-dependent manner, given that this effect was abrogated by treatment with antibody to mammalian TGF-β. We also show that host T-cells secrete elevated levels of the immunosuppressive cytokine IL-10 in response to metacestode E/S products. Within the E/S fraction of the metacestode we identified an E. multilocularis activin A homolog (EmACT) that displays significant similarities to mammalian Transforming Growth Factor-β (TGF-β/activin subfamily members. EmACT obtained from heterologous expression failed to directly induce Treg expansion from naïve T cells but required addition of recombinant host TGF-β to promote CD4+ Foxp3+ Treg conversion in vitro. Furthermore, like in the case of metacestode E/S products, EmACT-treated CD4+ T-cells secreted higher levels of IL-10. These observations suggest a contribution of EmACT to in vitro expansion of Foxp3+ Treg by the E. multilocularis metacestode. Using infection experiments we show that intraperitoneally injected metacestode tissue expands host Foxp3+ Treg, confirming the expansion of this cell type in vivo during parasite establishment.Conclusion/significanceIn conclusion, we herein demonstrate that E. multilocularis larvae secrete factors that induce the secretion of IL-10 by T-cells and contribute to the expansion of TGF-b-driven Foxp3+ Treg, a cell type that has been reported crucial for generating a tolerogenic environment to support parasite establishment and proliferation. Among the E/S factors of the parasite we identified a factor with structural and functional homologies to mammalian activin A which might play an important role in these activities.