Demographic and immune correlates of human herpesvirus 8 seropositivity in Malawi, Africa

Abstract

Background: In the USA, human herpesvirus 8 (HHV-8) is associated with Kaposi's sarcoma (KS) and HIV infection. We examined HHV 8 seroprevalence in a Malawian cohort, and assessed its relationship with HIV, KS, demographic characteristics, and immune findings. Methods: In 1997 and 1998, blood samples were obtained from 272 hospitalized Malawian patients, for whom demographic information was obtained, and 24 healthy volunteers without demographic data. We used enzyme immunoassays to assess seroprevalence and antibody titers to peptide antigens derived from HHV-8 K8.1 and ORF65-encoded proteins. Intracellular cytokines and cell surface antigens were assessed with four-color flow cytometry. Data were analyzed using non-parametric univariate and regression analytic techniques. Results: The rates of HHV-8 seroprevalence to either or both HHV-8 peptides were 67% for the patients and 54% for the healthy volunteers. Seroprevalence increased with patients' age (P<0.001) but was not associated with HIV status, percentage of lymphocytes expressing CD4, or KS (n=10). Seropositive females had lower antibody titers to both peptides than did males (medians: 455 versus 1361 for K8.1, P<0.001; and 268 versus 405 for ORF65, P=0.044). For the healthy volunteers, the percentage of CD8+ cells producing IFN-y after stimulation was significantly lower in ORF65-specific antibody-positive persons (medians: 24% versus 57%, P=0.008). Conclusions: In Malawi, HHV8 is endemic and is not associated with HIV infection or HIV severity. Seroprevalence rates increase in childhood, and, most steeply in adolescence. Titers are higher in seropositive males than in sero-positive females. The immune effects of HHV-8 in healthy adults are consistent with chronic inhibition of type 1 cytotoxic T -cell responsiveness, independent of HIV status.