nodes, or viscera, HHV-8-associated multicentric Castleman's disease – a lymphoproliferative disorder, Primary effusion lymphoma – KSHV-associated aggressive lymphoma involving B-cells that are immature plasma cells termed plasmablasts and regarded as one type of lymphoid neoplasms with plasmablastic differentiation, KSHV inflammatory cytokine syndrome – a syndrome with MCD-like symptoms but without associated pathology. Epidemiology In the 1970s, the global prevalence rate for HHV-8 is 2 to 10%. The seroprevalence of HHV-8 varies significantly geographically and infection rates in northern European, southeast Asian, and Caribbean countries are between 2-4%, in Mediterranean countries at approximately 10%, and in sub-Saharan African countries at approximately 40%. In South America, infection rates are low in general but are high among Amerindians. Even within individual countries, significant variation can be observed across different regions, with infection rates of about 19.2% in Xinjiang compared to about 9.5% in Hubei, China. Although seroprevalence has been consistently shown to increase with age in a linear manner, countries with high infection rates may see higher seroprevalence in younger age groups. Educational level has shown an inverse correlation with infection rates. Individuals infected with HIV-1 or genital warts are generally more likely to be co-infected with HHV-8. In countries with low seroprevalence, HHV-8 is primarily limited to AIDS and KS patients. In countries with high seroprevalence, infection is frequent in childhood, indicating a likely mother-to-child transmission by saliva. In a Zambian survey, all children with KS had mothers who were positive for HHV-8, whereas not all children whose mothers had KS were HHV-8 positive. In another Zambian survey, 13.8% of children were seropositive for HHV-8 by age 4. Seroprevalence has not been shown to vary significantly because of gender or marital status. Evolution The most recent common ancestor of this virus in the Mediterranean, Iran, and Xinjiang, China, has been estimated to have evolved 29,872 years (95% highest probability density 26,851-32,760 years) ago. the most recent common ancestor for viruses isolated in Xinjiang was 2037 years (95% highest probability density 1843–2229 years) ago. Given the historical links between the Mediterranean and Xinjiang during the Roman period it seems likely that this virus was introduced to Xinjiang along the Silk Road. The mutation rate was estimated to be 3.44 × 10−6 substitutions per site per year (95% highest probability density 2.26 × -6 to 4.71 × 10−6). However, the global distribution of different genotypes of KSHV and the potential transmission path need further