Latent class analysis of human herpesvirus 8 assay performance and infection prevalence in sub‐Saharan Africa and Malta

Abstract

Human herpesvirus 8 (HHV-8) is thought to be highly prevalent in Mediterranean countries and sub-Saharan Africa, where it causes Kaposi's sarcoma in a small proportion of infected immunocompetent persons. However, the lack of serological tests with established accuracy has hindered our understanding of the prevalence, risk factors and natural history of HHV-8 infection. We tested 837 subjects from Congo, Botswana (mostly young adults) and Malta (elderly adults), using an immunofluorescence assay and 2 enzyme immunoassays (EIAs, to viral proteins K8.1 and orf65). Each assay found HHV-8 seroprevalence to be high (49 -87%) in the African populations and generally lower (9 -54%) in Malta. However, there was only modest agreement among tests regarding which subjects were seropositive (3-way , 0.05-0.34). We used latent class analysis to model this lack of agreement, estimating each test's sensitivity and specificity and each population's HHV-8 prevalence. Using this approach, the K8.1 EIA had consistently high sensitivity (91-100%) and specificity (92-100%) across populations, suggesting that it might be useful for epidemiological studies. Compared with the K8.1 EIA, both the immunofluorescence assay and the orf65 EIA had more variable sensitivity (80 -100% and 58 -87%, respectively) and more variable specificity (57-100% and 48 -85%, respectively). HHV-8 prevalence was 7% among elderly Maltese adults. Prevalence was much higher (82%) in Congo, consistent with very high Kaposi's sarcoma incidence there. Prevalence was also high in Botswana (87% in Sans, an indigenous group, and 76% in Bantus), though Kaposi's sarcoma is not common, suggesting that additional co-factors besides HHV-8 are needed for development of Kaposi's sarcoma. Int.

Substantial regional differences in human herpesvirus 8 seroprevalence in sub‐Saharan Africa: Insights on the origin of the “Kaposi's sarcoma belt”

“…Overall, 42 (1.8%) of individuals were classified as equivocal in HHV-8 antibody testing and not considered in the primary analysis, leaving 471 participants in South Africa, 532 in Zimbabwe, and 1,330 in Uganda. Of those in the primary analysis, the median age was 28 years [interquartile range (IQR) [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] in South Africa, 29 years (IQR [25][26][27][28][29][30][31][32][33] (Table 1). The higher seroprevalence in Uganda did not substantially change throughout adulthood, only rising to 43.4% in those 41 years or older (p ¼ 0.30 for age trend).…”

The Impact of Preexisting or Acquired Kaposi Sarcoma Herpesvirus Infection in Kidney Transplant Recipients on Morbidity and Survival

“…The K8.1 EIA has been described in detail elsewhere ["http://www. journals.uchicago.edu/doi/full/10.1086/423326" \ l"rf18"] (9). In brief, serum samples were diluted 1:20 and added to ELISA plates that had been precoated with recombinant K8.1 protein.…”

Human herpesvirus 8 seroprevalence among Tobago women and the role of sexual lifestyle behavior

“…Human herpesvirus 8 (HHV-8), a member of the Family Herpesviridae and subfamily Gammaherpesvir-inae, is the causal agent of Kaposi's sarcoma (KS) and primary effusion lymphoma and has been associated with multicentric Castleman's disease [Chang et al, 1994;Cesarman et al, 1995;Soulier et al, 1995;Dupin et al, 1999]. HHV-8 seroprevalence varies geographically and is considered endemic in Mediterranean countries where seropositivity rates are as high as 31% in Southern Italy [Serraino et al, 2006], and in Sub-Saharan Africa, where seropositivity reaches 87% in Botswana Africa [Engels et al, 2000]. KS is relatively common in these areas: incidence is as high as 8.8 and 30 per 100,000 population per year in Italy and Sub-Saharan Africa, respectively [Engels et al, 2000;Vitale et al, 2001;Ferlay et al, 2004;Serraino et al, 2006].…”