HERPES SIMPLEX: PREGNANCY, NEONATAL RISK, HOST DEFENSE

新生儿HSV感染的发生率也在增加

The incidence of neonatal HSV infections is increasing in parallel with the increase in genital HSV infections. Preventing most cases of neonatal HSV infections depends upon avoiding contact with the virus at delivery. If lesions are present, delivery by cesarean section is indicated. Unfortunately, most neonatal infections result from exposure to asymptomatic maternal excretion of HSV, often by women with no past history of genital herpes. The failure of antepartum cultures to predict asymptomatic shedding at delivery in women with past recurrent genital herpes along with the fact that many mothers of infants with neonatal HSV have no history of genital herpes requires another approach to the problem of neonatal HSV. Most genital HSV infections are caused by HSV-2. Seroepidemiologic studies have been hampered by cross-reactivity between HSV-1 and 2 antigens until the development of serologic methods which detect antibodies to HSV-2 specific glycoproteins. We propose to investigate the value of taking viral cultures for HSV at all deliveries, regardless of maternal herpes history, and of HSV-2 specific serologic testing early and late in gestation. Past or recent HSV-2 infection will be determined by testing paired sera from the first prenatal visit and 28-32 weeks gestation using an ELISA method to detect antibodies to the HSV-2 glycoprotein G, which has HSV-2 specific epitopes. The frequency of HSV-2 infections in consecutive pregnant women with or without a history of genital HSV and the proportion which are primary infections will be assessed. Cultures will be obtained from all mothers and infants at delivery (approximately 5000/year). The sensitivity and specificity of shell vial culture and HSV antigen detection by enzyme immunofiltration for rapid diagnosis of neonatal HSV exposure will be compared with a standard tissue culture technique. The frequency of asymptomatic shedding of HSV at delivery among women with or without serologic evidence of past or recent HSV-2 infections will be determined. The frequency of prematurity, low birth weight, and/or evidence of intrauterine HSV infections among neonates born to mothers with serologic evidence of HSV-2 infections will be assessed. Much of the continued morbidity and mortality of neonatal HSV is due to delayed diagnosis. While delivery cultures will not prevent the exposure of infants to asymptomatic maternal HSV, identification of exposed infants should allow early diagnosis and immediate antiviral therapy of neonatal HSV. Infants known to be exposed to asymptomatic maternal HSV will be monitored to determine the frequency of subclinical and clinical HSV infections. Exposed neonates who do not contract HSV will be compared with HSV- infected neonates referred during the study period using assays for HSV neutralizing antibody, antibody mediating cellular cytotoxicity and antibodies to HSV glycoproteins. The failure of antepartum cultures to predict and therefore prevent neonatal exposures to HSV at delivery has made it critical to develop a rational approach to the problem of neonatal HSV infections.