HSV neutralizing antibodies further refinement in preventing neonatal Herpes infection

Abstract

The immune system of the fetus and newborn is immature in the immediate period before and after birth. Therefore, transferable maternal immune memory through maternal neutralizing antibodies is essential for the survival of the fetus, newborn, and infant. 1 The typical maternal immunologic reaction following microbial infection is the early specific production of IgG antibodies. Antibody avidity is low after primary infection but matures slowly within weeks and increases progressively as a function of time after antigenic exposure. 2 These antibodies enter the fetal circulation through the placenta. Maternal antibody avidity testing has been applied successfully for the diagnosis of perinatal infections for human immunodeficiency virus, cytomegalovirus, and toxoplasmosis. Presence of these antibodies has been shown to be predictive of the risk of vertical transmission. 3-5 Low or absent antibody avidity levels are characteristic of primary infection and increase risk of neonatal infection. Although high, antibody avidity levels are characteristic of established infection and decrease risk of newborn infection. Development of herpes simplex virus (HSV) antibody avidity testing has been an area of ongoing investigation. Development and use of a type specific antibody avidity test for HSV-2 using sera from women with recently acquired and established genital HSV-2 has been reported. 6 Development of specific antibody avidity test for HSV-1 is imperative because approximately one third of the cases of neonatal herpes are caused by this virus. HSV antibody avidity testing in pregnant women with genital herpes may help refine the risk of acquisition of neonatal infection and help target current prevention strategies. These strategies assume increasing importance in light of the rapid growth of cases of HSV infection in women in the United States. The prevalence of genital and neonatal herpes continues to rise in the United States. According to the Centers for Disease Control and Prevention, 1 of 4 women in the United States is infected with HSV-2. Since the late 1970s, the number of cases of genital herpes infection in the United States has increased 30% nationwide. The fastest growing subgroups with infection are women of reproductive age. 7 Because neonatal HSV infection is not reportable, exact prevalence data are difficult to obtain. Neonatal HSV infection occurs in 1 in 2500 to 5000 deliveries. Neonates have the highest risk of developing HSV visceral infection and encephalitis. Without prompt effective treatment, 70% of infected neonates will progress to disseminated or central nervous system disease. Most neonatal infections are due to HSV-2, although 30% of cases are caused by HSV-1. HSV-1 appears to possess a higher efficiency of transmission from mother to infant. The risk of transmission of HSV to neonates is 30% to 50% when genital herpes is acquired near labor, whereas it is less than 1% when neonatal exposure results from reactivation HSV at delivery. 8 The major obstacle to formulating an effective prevention strategy for neonatal HSV is that the majority of infected infants are born to mothers who are asymptomatic at delivery and have no history of genital herpes. Therefore, strategies that are implemented late in pregnancy are particularly attractive and offer promise to help reduce neonatal HSV infection.