The cyclophilin inhibitor Debio 025 combined with PEG IFNalpha2a significantly reduces viral load in treatment-naïve hepatitis C patients.

UNLABELLED: The anti-hepatitis C virus (HCV) effect and safety of three different oral doses of the cyclophilin inhibitor Debio 025 in combination with pegylated interferon-alpha2a (PEG IFN-alpha2a) were investigated in a multicenter, randomized, double-blind, placebo-controlled escalating dose-ranging phase II study in treatment-naïve patients with chronic hepatitis C. Doses of 200, 600, and 1,000 mg/day Debio 025 in combination with PEG IFN-alpha2a 180 microg/week for 4 weeks were compared with monotherapy with either 1,000 mg/day Debio 025 or 180 microg/week PEG IFN-alpha2a. In patients with genotypes 1 and 4, the 600- and 1,000-mg combination treatments induced a continuous decay in viral load that reached -4.61 +/- 1.88 and -4.75 +/- 2.19 log(10) IU/mL at week 4, respectively. In patients with genotypes 2 and 3, HCV RNA levels at week 4 were reduced by -5.91 +/- 1.11 and -5.89 +/- 0.43 log(10) IU/mL, respectively, with the same treatment regimens. Adverse events were comparable between treatment groups apart from a higher incidence of neutropenia associated with PEG IFN-alpha2a and an increased incidence of isolated hyperbilirubinemia at the highest dose of Debio 025 (1,000 mg/day). CONCLUSION: These results confirm that Debio 025 has a potent activity and an additive effect on HCV RNA reduction in genotype 1 and 4 patients at 600 and 1,000 mg/day when combined with PEG IFN-alpha2a.

PCR detection and serological evidence of granulocytic ehrlichial infection in roe deer (Capreolus capreolus) and chamois (Rupicapra rupicapra).

The role of wild mammals, such as roe deer (Capreolus capreolus) and chamois (Rupicapra rupicapra), in the epidemiology of granulocytic ehrlichiae in Switzerland was investigated. We tested blood samples for Ehrlichia phagocytophila genogroup 16S rRNA gene sequences by PCR and for immunoglobulin G antibodies against granulocytic ehrlichiae by indirect fluorescent-antibody assay (IFA). Overall means of 60.9% of 133 roe deer serum samples and 28.2% of 39 chamois serum samples were seroreactive by IFA. PCR results were positive for 18.4% of 103 roe deer serum samples as well. None of the 24 chamois blood samples tested were positive by PCR. Partial 16S rRNA gene and groESL heat shock operon sequences of three roe deer samples tested showed strong degrees of homology (> or =99.7 and > or =98.6%, respectively) with the sequences of granulocytic ehrlichiae isolated from humans. These results confirm that chamois, and particularly roe deer, are commonly infected with granulocytic ehrlichiae and provide evidence that these wild mammals are potential reservoirs for granulocytic ehrlichiae in Switzerland.