Cervicovaginal levels of lactoferrin, secretory leukocyte protease inhibitor, and RANTES and the effects of coexisting vaginoses in human immunodeficiency virus (HIV)-seronegative women with a high risk of heterosexual acquisition of HIV infection.

Innate immune factors in mucosal secretions may influence human immunodeficiency virus type 1 (HIV-1) transmission. This study examined the levels of three such factors, genital tract lactoferrin [Lf], secretory leukocyte protease inhibitor [SLPI], and RANTES, in women at risk for acquiring HIV infection, as well as cofactors that may be associated with their presence. Women at high risk for HIV infection meeting established criteria (n = 62) and low-risk controls (n = 33) underwent cervicovaginal lavage (CVL), and the CVL fluid samples were assayed for Lf and SLPI. Subsets of 26 and 10 samples, respectively, were assayed for RANTES. Coexisting sexually transmitted infections and vaginoses were also assessed, and detailed behavioral information was collected. Lf levels were higher in high-risk (mean, 204 ng/ml) versus low-risk (mean, 160 ng/ml, P = 0.007) women, but SLPI levels did not differ, and RANTES levels were higher in only the highest-risk subset. Lf was positively associated only with the presence of leukocytes in the CVL fluid (P < 0.0001). SLPI levels were lower in women with bacterial vaginosis [BV] than in those without BV (P = 0.04). Treatment of BV reduced RANTES levels (P = 0.05). The influence, if any, of these three cofactors on HIV transmission in women cannot be determined from this study. The higher Lf concentrations observed in high-risk women were strongly associated with the presence of leukocytes, suggesting a leukocyte source and consistent with greater genital tract inflammation in the high-risk group. Reduced SLPI levels during BV infection are consistent with an increased risk of HIV infection, which has been associated with BV. However, the increased RANTES levels in a higher-risk subset of high-risk women were reduced after BV treatment.

HIV-1 target cells in foreskins of African men with varying histories of sexually transmitted infections.

Numerous epidemiologic studies have found significant associations between lack of circumcision and HIV-1 acquisition in men. To our knowledge, this is the first study of human foreskin tissue that examines biologic mechanisms that increase susceptibility of uncircumcised African men to HIV-1. Foreskin specimens from 20 men with and 19 men with no history of sexually transmitted infections were examined for HIV-1 target cells. Most Langerhans cells were found in the epithelium; most CD4+ T cells and macrophages were in the submucosa. There were no differences in HIV-1 target cells between men with and those without history of sexually transmitted infections. However Langerhans cells and macrophages were more abundant in the group with a history of infection. The densities and positions of HIV-1 target cells in the foreskin tissue of these Kenyan men indicate that the inner mucosal surface of the human foreskin contains cells that make it highly susceptible to HIV infection.

The public health imperative for a neonatal herpes simplex virus infection surveillance system.

About 1 in 5 sexually active adults in the United States has serologic evidence of genital herpes caused by herpes simplex virus type-2. Neonatal herpes simplex virus infection is a serious consequence of genital herpes infection. Herpes infection in neonates causes significant morbidity and neurologic damage and generally has a case-fatality ratio untreated of 60%. It is estimated that 440 to 1,320 cases of neonatal herpes infections occur in the United States per year (11-33 cases occur per 100,000 live births). Given the challenges in surveillance for genital herpes due to the large number of asymptomatic infections and infrequent laboratory-based diagnosis, we recommend that to begin an effective national control program for herpes infections, a mandatory national surveillance system for neonatal herpes be implemented. Such a system would help assure appropriate therapy, help monitor trends and understand the burden of disease, identify risk determinants, and evaluate prevention efforts.