States. This article will review the changing epidemiology of genital and neonatal HSV infections with emphasis on the current status of therapy of the newborn, the cost of disease to society, and the need for the development of appropriate preventive strategies. Since the infected newborn is most likely to develop life-threatening disease and, therefore, incur the greatest costs to society, the baby becomes the starting point for our considerations.
Although centers in the United States caring for infants with neonatal HSV infections have observed fluctuations in disease incidence, the estimated rate of occurrence is approximately 1 in 2500 to 1 in 5000 deliveries yearly (7–9). For unknown reasons, several countries worldwide, such as Africa and the United Kingdom, do not appear to recognize a significant number of cases of neonatal HSV infection in spite of the high prevalence of antibodies to HSV-2 (10, 11). In fact, the incidence of neonatal HSV infections in the United States may reflect the decreasing prevalence of HSV-1 antibodies and, therefore, the absence of transplacental humoral immunity, which might confer protection to the fetus.
At least four factors influence the incidence of newborn HSV disease. The first is the type of maternal genital infection at the time of delivery. The duration and quantity of viral excretion and the time to total healing vary with primary, initial, and recurrent maternal genital infections, such that primary, initial, and recurrent maternal genital infections, such that primary is most and recurrent is least severe (12, 13). Primary infection is associated with the excretion of 106–108 plaque-forming units of HSV for as long as 14–21 days. In contrast, recurrent infection is associated with a shorter duration of viral excretion (namely, 3–5 days) and at lower quantities (about 102 plaque-forming units of HSV). The incidence of neonatal herpes in babies born to women with primary or initial genital HSV infection is higher (33%) than those with recurrent infection (3%) (14). Second, the mother's HSV antibody status at delivery influences the severity of maternal infection as well as the likelihood of transmission. Transplacental maternal neutralizing and antibody-dependent cell-mediated cytotoxic (ADCC) antibodies have at least an ameliorative effect on acquisition and severity of infection for babies exposed to virus (15–18). Maternal primary infection late in gestation usually does not result in significant passage of maternal transplacental antibodies and, therefore, will increase risk to the fetus