The Long-Term Clinical and Economic Impact of Universal Varicella Vaccination in Slovenia.

Background: Despite the substantial burden of varicella infection, Slovenia does not currently have a universal varicella vaccination (UVV) program. We modeled the long-term clinical and economic impact of implementing 2-dose UVV strategies compared with no vaccination in Slovenia. Methods: A previously published dynamic transmission model was adapted to the demographics, varicella seroprevalence, herpes zoster incidence, and contact patterns in Slovenia. Six 2-dose UVV strategies, vs no vaccination, were considered over a 50-year period, including monovalent vaccination (Varivax® [V-MSD] or Varilrix® [V-GSK]) at ages 12 and 24 months, or monovalent vaccination at 15 months followed by monovalent or quadrivalent vaccination (ProQuad® [MMRV-MSD] or Priorix- Tetra® [MMRV-GSK]) at 5.5 years. Costs, quality-adjusted life-years, and incremental cost-effectiveness ratios vs no vaccination were calculated to assess the economic impact of each strategy from payer and societal perspectives. Results: The incidence of varicella infection was estimated as 1228 per 100 000 population in the absence of UVV. Over 50 years, depending on vaccination strategy, UVV reduced varicella cases by 77% to 85% and was associated with substantial reductions in varicella deaths (39%-44%), outpatient cases (74%-82%), and hospitalizations (74%-82%). The greatest reductions were predicted with V-MSD (15 months/5.5 years) and V MSD/MMRV-MSD (15 months/5.5 years). Discussion: All 2-dose UVV strategies were cost-effective compared with no vaccination from payer and societal perspectives, with V-MSD (15 months/5.5 years) being the most favorable from both perspectives. Conclusion: Policymakers should consider implementing UVV to reduce the burden of varicella disease in Slovenia.

Aspects of the progesterone response in Hortaea werneckii: Steroid detoxification, protein induction and remodelling of the cell wall.

Progesterone in sublethal concentrations temporarily inhibits growth of Hortaea werneckii. This study investigates some of the compensatory mechanisms which are activated in the presence of progesterone and are most probably contributing to escape from growth inhibition. These mechanisms lead on the one hand to progesterone biotransformation/detoxification but, on the other, are suggested to increase the resistance of H. werneckii to the steroid. Biotransformation can detoxify progesterone efficiently in the early logarithmic phase, with mostly inducible steroid transforming enzymes, while progesterone biotransformation/detoxification in the late logarithmic and stationary phases of growth is not very efficient. The relative contribution of constitutive steroid transforming enzymes to progesterone biotransformation is increased in these latter phases of growth. In the presence of progesterone, activation of the cell wall integrity pathway is suggested by the overexpression of Pck2 which was detected in the stationary as well as the logarithmic phase of growth of the yeast. Progesterone treated H. werneckii cells were found to be more resistant to cell lysis than mock treated cells, indicating for the first time changes in the yeast cell wall as a result of treatment with progesterone.