title: Identifying human herpesvirus 8 infection: performance characteristics of serologic assays.
abstract: Epidemiologic studies of infection with the oncogenic human herpesvirus 8 (HHV-8) depend on serologic methods to diagnose infection. However, optimal strategies for identifying HHV-8 infection remain undefined. We therefore evaluated four enzyme-linked immunoassays (EIAs) and one immunofluorescence assay (IFA) using sera from 87 individuals with the prototype HHV-8 disease, Kaposi's sarcoma (KS), and 210 participants in a hemophilia study (who were presumed not to be infected with HHV-8). Assays performed reasonably well in distinguishing between infected and uninfected persons, with receiver operator curve areas between 0.86 and 0.96. Nonetheless, IFA had only 86% sensitivity and 88% specificity, and no EIA simultaneously had sensitivity and specificity above 90% for any of the optical density (OD) cutpoints used to define seropositivity. Some assays were markedly less sensitive with diluted KS sera, suggesting that they poorly identify low-titer antibodies present in asymptomatic infection. We also developed a classification tree that categorized individuals as seropositive if they had OD > 2.00 on recombinant K8.1 protein EIA or if they had both K8.1 OD between 0.51 and 2.00 and positive IFA results; this strategy had between 80% and 90% sensitivity and 95% and 100% specificity. Overall, assays performed adequately for use in most epidemiologic investigations, but wider applications will require improved tests.
authors.affiliation: Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20852, USA. engelse@exchange.nih.gov
authors.forename: E A
authors.initials: EA
authors.lastname: Engels
authors.forename: D
authors.initials: D
authors.lastname: Whitby
authors.forename: P B
authors.initials: PB
authors.lastname: Goebel
authors.forename: A
authors.initials: A
authors.lastname: Stossel
authors.forename: D
authors.initials: D
authors.lastname: Waters
authors.forename: A
authors.initials: A
authors.lastname: Pintus
authors.forename: L
authors.initials: L
authors.lastname: Contu
authors.forename: R J
authors.initials: RJ
authors.lastname: Biggar
authors.forename: J J
authors.initials: JJ
authors.lastname: Goedert
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis / Q000821:virology; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D005069:Evaluation Studies as Topic; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006467:Hemophilia A; D019288:Herpesvirus 8, Human / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D012372:ROC Curve; D012514:Sarcoma, Kaposi / Q000175:diagnosis* / Q000821:virology; D012680:Sensitivity and Specificity
chemical_list: D000914:Antibodies, Viral