Background Kaposi sarcoma-associated herpesvirus (KSHV) is the causal agent for Kaposi sarcoma (KS) and multicentric Castleman disease (MCD) in HIV-infected patients. Patients with KSHV-MCD develop fevers, wasting, hypoalbuminemia, cytopenias, and hyponatremia that are related to overproduction of KSHV-encoded vial interleukin (IL)-6 (vIL-6) and human IL-6. Methods We identified 6 HIV-infected patients with KS or serological evidence of KSHV infection who had severe inflammatory MCD-like symptoms but in whom we could not diagnose MCD, and hypothesized that these symptoms resulted from vIL-6 overproduction. Serum vIL-6 levels were assessed in these 6 patients and compared to 8 control patients with symptomatic KSHV-MCD and 32 control patients with KS. KSHV viral load, serum human IL-6 (hIL-6), and human IL-10 were also evaluated. Results Patients with inflammatory MCD-like symptoms but without MCD had elevated vIL-6 levels comparable to patients with symptomatic KSHV-MCD and significantly greater than control patients with KS (P = 0.0026). Elevated hIL-6, IL-10, and KSHV viral loads were also comparable to patients with symptomatic KSHV-MCD and significantly greater than those with KS. Conclusions A subset of patients with HIV and KSHV co-infection, but without MCD, can develop severe systemic inflammatory symptoms associated with elevated levels of KSHV vIL-6, IL-6, and KSHV viral loads. Excess lytic activation of KSHV, production of the lytic gene product vIL6, and associated immunologic dysregulation may underlie the pathophysiology of these symptoms. This IL-6-related inflammatory syndrome is important to consider in critically ill patients with HIV and KSHV co-infection.

Human herpesvirus 8 (HHV-8) epidemiology in Brazilian Amerindians was studied. Use of an immunofluorescence (IFA) test for latent antibody demonstrated that the prevalence of HHV-8 in 781 Amerindians of diverse tribes (overall, 53% prevalence) was not related to language group or sex but rather increased gradually from 41% in children <10 years of age to 65% in adults >/=30 years of age. In IFA-positive subjects, HHV-8 DNA was detected in 3 (16%) of 19 mononuclear cell samples from peripheral blood and in 1 of 16 saliva samples. The sequences of conserved ORF22 and K6 genes were typical of HHV-8, but the variable K1 gene sequences were only 70%-75% identical to other known HHV-8 strains. Thus, a new HHV-8 subtype, E, is hyperendemic in Brazilian Amerindians, although Kaposi's sarcoma has not been reported. Transmission is probably oral rather than sexual. The limited genetic pool in isolated groups may permit more frequent transmission of a virus with a low prevalence in heterogeneous populations.

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