Neonatal herpes continues to be the most devastating consequence of genital herpes infections, with afrequency that has not declined in the last several decades. Yet no prevention strategies have beenimplemented. The risk of HSV transmission is highest among women who have newly acquired HSV-2 orHSV-1 in the genital tract and who are seronegative; the risk is also high among HSV-1 seropositive womenwho have newly acquired HSV-2 or reactivation of HSV-1; the risk is low in women with established HSV-2infection. Genital HSV shedding at the time of delivery is associated with a relative risk of >300 for HSVtransmission. We have developed a sensitive and specific HSV DMA PCR that can be resulted within 2hours of obtaining the sample; the test is completing validation studies for implementation for routine use inthe University of Washington Hospital Clinical Laboratories. We propose to use this assay to develop astrategy to detect the infant exposed to HSV at delivery and to evaluate the feasibility of implementinginterventions to reduce the risk of HSV-1 and HSV-2 infections in the exposed newborns.
Specific Aim 1 isto determine the incidence of exposure of the neonate to HSV at the time of delivery. We hypothesizethat HSV DMA detection by PCR, in combination with HSV serologic testing (performed routinely in pregnantwomen at the University of Washington), will accurately define HSV-exposed infants at high versus low riskof developing neonatal herpes. This information will be utilized by the medical team to reduce the risk of HSVinfection either through obstetrical practices (C-section, reduced use of fetal monitoring devices, use of IVacyclovir) or subsequent management of the HSV exposed infant.
Specific Aim 2 will evaluate thefeasibility of intrapartum intravenous acyclovir, followed by oral acyclovir to the neonate, as anapproach for managing HSV-2 seropositive women who shed HSV at delivery and their infants whoare exposed to HSV during birth. We hypothesize that IV acyclovir given to women in labor will result intherapeutic levels of acyclovir in the cord blood, and that oral administration of acyclovir to the newborn willbe feasible, as evaluated by clinical and laboratory measures, and acceptable to pediatricians and parents.This approach shifts the current paradigm for prevention of neonatal herpes from the women with clinicaldisease to the detection and management of the infant exposed to subclinical infection at delivery. Theproject will for the first time collect data on current American Academy of Pediatrics guidelines for HSVexposed infants and develop tools for prevention of neonatal HSV that can be tested in multicenter trials.Neonatal herpes is a serious disease among newborns. The project will develop tools to identify newbornsexposed to HSV at birth at risk and develop optimal care for newborns who are at risk for neonatal herpes.
Showing the most recent 10 out of 345 publications
