The potential epidemiological impact of a genital herpes vaccine for women.

BACKGROUND: In two phase III vaccine trials immunisation of women previously uninfected by herpes simplex virus provided protection against genital herpes disease. In deciding policy, an evaluation of the epidemiological impact of the partial protection provided by the vaccine should be considered. METHODS: A sex and sexual activity stratified deterministic differential and partial differential equation model of the natural history of herpes simplex virus type 2 (HSV-2) and the impact of vaccination is developed and analysed. To explore the role of vaccination, the pattern of viral shedding and the transmission of infection during sexual acts within sexual partnerships are described. RESULTS: Using literature derived estimates of parameter values and assuming efficacy in only 40% of women the impact of the vaccine depends on assumptions made about its action. The vaccine has a limited impact if it only prevents disease but a more substantial impact if it reduces asymptomatic viral shedding, which it could do indirectly by preventing infection or directly by modifying the biology of the infection. Concern over the implications of a vaccine that prevents disease but has no impact on viral shedding was addressed in a worst case scenario. Here there is a modest increase in the incidence of infection in both men and women but an increase in disease prevalence in men alone, since the virus directly protects some women from disease. CONCLUSIONS: Results suggest that a herpes vaccine should be used universally and that a vaccine that only protects HSV-1-/2- women can paradoxically have a significant epidemiological impact, the scale of which depends upon changes in patterns of viral shedding.

Results of a Meta-Analysis of Trapidil, a PDGF Inhibitor Ñ A Sufficient Reason for a Second Look to the Pharmacological Approach to Restenosis.

Restenosis in 30%Ð40% of patients remains the major limitation to the long-term success of balloon angioplasty (PTCA) in patients with coronary artery disease. So far, only coronary stent implantation has established its role as an effective strategy to prevent restenosis after PTCA. In contrast to numerous pharmacological strategies that all have failed to demonstrate a convincing reduction in the rate of restenosis, trapidil, a PDGF inhibitor, has shown promising and conclusive results in animal models as well as in three human trials published between 1992 and 1994. Although the results of the human trials showed trapidil to be capable of reducing restenosis after PTCA by 40%Ð53% compared to control patients, the compound is not well known and little used in interventional cardiology. Possible explanations for this situation may include trapidilÕs non-availability in the United States and most European countries, the small number of trapidil trials and treated patients, as well as a probable perception of the medical community that a pharmacological approach to restenosis prevention is unlikely to work. Additionally, clinical expert behavior has often shown not to be synchronized with accumulating evidence of efficacy. The results of this meta-analysis, however, demonstrate trapidilÕs efficacy. The rate of per-patient restenosis in the trapidil group was more than halved as compared to controls (odds ratio 0.44, 95% confidence interval 0.29Ð0.66). Tolerability with trapidil was good, and the rare adverse events observed included gastric intolerance, thrombocytopenia, headache, and increased serum AST and ALT levels which were transient or subsided with cessation of treatment.