Abstract

The ability to readily and accurately diagnose Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus 8) infection in individuals remains a demanding task. Among the available diagnostic methods, sensitivities and specificities range widely, and many are inadequate for large-scale screening studies. We examined a serological algorithm for detecting KSHV in human sera having high sensitivity and specificity. This method uses previously described open reading frame (ORF) K8.1 and ORF65 peptide-based enzyme-linked immunosorbent assays and a novel purified recombinant full-length LANA1 protein. We generated two multiantigen algorithms: one that maximized sensitivity and one that maximized specificity. These serological algorithms were then used to evaluate seroprevalence rates among populations of clinical and epidemiological importance. The serological algorithms yielded sensitivities of 96% and 93% and specificities of 94% and 98% for the more sensitive and specific algorithms, respectively. Among kidney donors, seroprevalence was low, 4.0% (2/50), and similar to that of blood donors (P = 0.46; odds ratio [OR], 1.4; confidence interval [CI], 0.14 to 7.9) using the highly specific algorithm. Using the sensitive algorithm, 8.0% (4/50) were infected compared to 6.4% (16/250) observed among blood donors (OR, 1.3; CI, 0.41 to 4.0; P = 0.43). Among subjects requiring bone marrow transplantation, seroprevalence rates were not elevated compared to those of blood donors (OR, 2.0; 95% CI, 0.10 to 122.9; P = 0.50). Because the need for high-quality KSHV detection methods are warranted and because questions remain about the optimal methods for assessing KSHV infection in individuals, we propose a systematic approach to standardize and optimize the assessment of KSHV infection rates using a combination of established and novel serological assays and methods.