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Developing therapeutic strategies for prevention of neonatal herpes : antivirals and microbicides Leung, Daniel Ted

Abstract

Genital herpes is a sexually transmitted disease affecting many women of childbearing age. Recurrences during childbirth can result in transmission to the neonate. The current strategy to prevent neonatal herpes has focused on the use of suppressive acyclovir therapy in late pregnancy. Issues pertaining to the safety, efficacy, and cost-effectiveness of this treatment were evaluated in our investigation. To examine the potential myelosuppressive effects of acyclovir use in late pregnancy, a clinical trial protocol was developed and implemented. A lack of enrolment in this placebo-controlled study led to inconclusive results. However, quantitative analysis of cord blood samples from the same patients revealed that although adequate blood levels are achieved with most patients at delivery, a longer duration of labor was correlated with lower levels. Inadequate levels of acyclovir could result in reactivation and viral shedding, thus endangering the neonate. Therefore, issues of noncompliance and vomiting during labor need to be addressed. For this investigation, a sensitive and rapid analytical assay with small volume requirements was developed and validated for the detection of acyclovir in plasma using capillary electrophoresis technology. With solid phase extraction and ultraviolet detection, the limit of quantification and the limit of detection was 20 ng/ml and 5.5 ng/ml, respectively. Suppressive acyclovir use in pregnancy was demonstrated to be cost-effective in a Canadian context, with most of the savings due to the avoidance of caesarean sections. This therapy was found to be especially cost effective in women with greater than 6 recurrences per year. Finally, the use of dendrimers as vaginal microbicides was proposed as an alternative strategy for the prevention of neonatal herpes. In vitro studies demonstrated that this class of compounds acts on both early and late stages of herpes simplex virus replication, making it a suitable candidate as an adjunct to existing oral antiviral therapy.

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