Respective Roles of Serological Status and Blood Specific Antihuman Herpesvirus 8 Antibody Levels in Human Herpesvirus 8 Intrafamilial Transmission in a Highly Endemic Area

Abstract

Transmission of human herpesvirus 8 (HHV-8), the etiological agent of Kaposi's sarcoma, occurs mainly during childhood in endemic countries and, to a large extent, through intrafamilial contacts. To additionally investigate this familial transmission, and especially the role of plasma anti-HHV-8 antibody titers, we conducted a large survey in a village from Cameroon, Central Africa, including 92 families (608 individuals). Plasma samples were tested for specific IgG directed against HHV-8 lytic antigens by immunofluorescence assay, and titers were determined by 2-fold dilutions. Global HHV-8 seroprevalence was 60%, raising from 32% under 9 years up to a plateau of around 62% between 15 and 40 years. The familial correlation patterns in HHV-8 seropositive/seronegative status showed strong dependence from mother to child and between siblings. In contrast, no familial correlation in anti-HHV-8 antibody levels was observed among infected subjects. In particular, no relationship was observed between the anti-HHV-8 antibody titer of HHV-8 seropositive mothers and the proportion of their HHV-8 seropositive children. Furthermore, a random permutation study of the anti-HHV-8 antibody titers among HHV-8 infected subjects showed that the main risk factor for infection was the HHV-8 serologic status and not the antibody level. In addition, no correlation was found between anti-HHV-8 antibody levels and buffy coat HHV-8 viral loads in a subsample of 95 infected subjects. Overall, these results strongly suggest that, in this highly endemic population from Central Africa, HHV-8 transmission mainly occurs from mother to child and between siblings, and it is independent of plasma antibody levels of HHV-8 infected relatives.

A major locus on chromosome 3p22 conferring predisposition to human herpesvirus 8 infection

“…9,21 This test which detects antibodies directed principally against lytic HHV-8 antigens is very suitable for use in epidemiologic studies and does not react with any other known HHV-8, including Epstein-Barr virus. It has been used by many groups leading to epidemiological results on HHV-8 that have been widely confirmed by different studies using the same or additional serological tests.…”

“…Six studies have provided evidence of correlated HHV-8 serological status between mother and children, one in a Jewish population from Israel 6 and five in the populations of African origin. [7][8][9][10][11] Three of these studies investigating dependences between other biological relatives also found that HHV-8 serological status was strongly correlated between siblings. [8][9][10] This pattern of familial aggregation, which is not accounted for by known risk factors, suggests that host genetic factors may be involved in HHV-8 infection.…”

“…[7][8][9][10][11] Three of these studies investigating dependences between other biological relatives also found that HHV-8 serological status was strongly correlated between siblings. [8][9][10] This pattern of familial aggregation, which is not accounted for by known risk factors, suggests that host genetic factors may be involved in HHV-8 infection. This hypothesis was supported by a segregation analysis identifying a recessive gene controlling HHV-8 infection in the children of African origin living in French Guiana.…”

“…9 This work was carried out as a part of a multidisciplinary project (anthropological, medical, and economic) in which all the individuals living in this village were studied. All the subjects live in very similar conditions in dwellings close to each other, and have very homogeneous cultural and social behaviors, which allow assuming a similar level of exposure to HHV-8 for all study subjects.…”

The Viral Etiology of AIDS‐Associated Malignancies

“…In these countries, the seroprevalence of KSHV in different risk groups mirrors the incidence of AIDS-KS, with a seroprevalence rate of between 25% and 50% among homosexual men. On the contrary, the reported seroprevalence of KSHV is high in the adult general population in regions of Brazil, French Guiana, the Mediterranean basin, and Central and Southern Africa, where it ranges from 10% to over 80%; these regions are considered endemic for KSHV (Cunha et al, 2005;Freitas et al, 2002;Kazanji et al, 2005;Klaskala et al, 2005;Mayama et al, 1998;Mbulaiteye et al, 2003;Olsen et al, 1998;Plancoulaine et al, 2000Plancoulaine et al, , 2004Wilkinson et al, 1999). Central African countries, like the Republic of Congo, Uganda, and Zambia, also have the highest KSHV infection rates in the world .…”