Human herpesvirus 8 primary infection occurs during childhood in Cameroon, Central Africa

Abstract

While in the United States and northern Europe, human herpesvirus 8 (HHV-8) appears to be mainly sexually transmitted with primary infection occurring in adulthood, the modes of transmission remain unknown in East and Central Africa, where Kaposi's sarcoma (KS) is a long-standing endemic disease, occurring not only in adults but also in children. The aim of our present study was to determine the prevalence of HHV-8 infection in children from Yaoundé , Cameroon, Central Africa. Specific antibodies directed against both latent and lytic HHV-8 antigens were detected and titrated, with an immunofluorescence assay using the KS-1 cell line, in the plasma of 258 children and adolescents, of 32 mother and child pairs and of 189 pregnant women. Two different HHV-8 DNA-specific sequences were searched in the buffy coat by PCR assays. The overall HHV-8 seroprevalence was 27.5% among these children and adolescents. In newborns, seroprevalence reached 46%, reflecting passive transmission of maternal IgG. This was followed by a marked drop. Then, beginning around 4 years of age, a regular increase of HHV-8 antibodies took place, reaching 39% in the 12-to 14-year age group and 48% above 15 years, a rate similar ( Kaposi's sarcoma-associated herpesvirus (KSHV), now named human herpesvirus 8 (HHV-8), was uncovered in 1994 in Kaposi's sarcoma (KS) skin lesions as foreign DNA sequences absent from healthy skin tissue (Chang et al., 1994). Very rapidly, the complete sequence of this new human gamma herpesvirus was obtained and indicated the presence of sequence homologies with 2 known herpesviruses, namely, Epstein-Barr Virus (EBV) and herpesvirus saimiri (HVS), both oncogenic, but also with human genes involved in the control of cell mitosis. HHV-8, which has been detected in every studied case of KS whether of the classic, endemic, epidemic, post-transplant or pediatric form (Buonaguro et al., 1996;Chang et al., 1994;Moore et al., 1996;Kasalo et al., 1997), is now considered the etiological agent of this tumor. This virus has further been associated with primary effusion lymphomas (Gessain et al., 1997) and a subset of multicentric Castleman's disease (Gessain et al., 1996). The availability of specific and sensitive serological assays, developed from different sources, allows epidemiological surveys.Based on the few available studies (Simpson et al., 1996;Gao et al., 1996;Kedes et al., 1996;Lennette et al., 1996;Martin et al., 1998;Melbye et al., 1998;Calabro et al., 1997; Withby et al., 1998), it appears that HHV-8 is not a worldwide, ubiquitous virus and that its level of endemicity correlates with the prevalence rates of KS in a given population or geographical area. Thus, while in the United States and the United Kingdom HHV-8 infection seems quite rare in the general population (1% to 5% of HHV-8-seropositive blood donors) and KS occurrence is very low, the situation is different in southern Italy and Greece, where HHV-8 exhibits higher prevalence together with the classic form of KS

Review of the distribution of Kaposi's sarcoma-associated herpesvirus (KSHV) in Africa in relation to the incidence of Kaposi's sarcoma

“…Of these, three studies identified evidence of KSHV-DNA in peripheral blood cells (Chang et al, 1996;Kasolo et al, 1997;Belec et al, 1998), two used a lytic antibody assay alone (He et al, 1998;Lampinen et al, 2000), five used a latent antibody assay alone Ariyoshi et al, 1998;Bestetti et al, 1998;Bourboulia et al, 1998;Sitas et al, 1999) and 18 used both a lytic and a latent assay (Lennette et al, 1996;Simpson et al, 1996;Mayama et al, 1998;Olsen et al, 1988;Ablashi et al, 1999;Andreoni et al, 1999Andreoni et al, , 2002Enbom et al, 1999;Gessain et al, 1999;Wilkinson et al, 1999;Engels et al, 2000;Rezza et al, 2000;Gaye Serraino-Diallo et al, 2001;Kakoola et al, 2001;Nuvor et al, 2001;Serraino et al, 2001;Wawer et al, 2001). The results are presented in Table 1, together with the estimated cumulative incidence of Kaposi's sarcoma in men aged 0 -64 years in the period before HIV infection (Cook-Mozaffari et al, 1998).…”

Seroprevalence of human herpesvirus-8 (HHV-8) in countries of Southeast Asia compared to the USA, the Caribbean and Africa

“…Current data indicate that HHV-8 infection is more prevalent in countries where classic and endemic KS occurs . In these countries, horizontal transmission and mother-to-child transmission are likely to occur (Bourboulia et al, 1998;Luppi et al, 1998;Gessain et al, 1999). In countries with a low incidence of classic or endemic KS, HHV-8 is predominantly found in homosexual men at risk of developing KS Martin et al, 1998;Verbeek et al, 1998), and is a sexually transmitted agent among these individuals (Martin et al, 1998).…”

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

“…They provided controversial results, although generally in favor of the absence of correlation (28 -30). Another study done in Cameroon also showed no difference in specific antibody titers of HHV-8 infected children according to their negative/ positive status for detection of HHV-8 DNA by PCR in the blood (10). However, two studies in South Africa (31,32) concluded that the proportion of HHV-8 infected children increased with increasing maternal antibody titers, suggesting a possible correlation between anti-HHV8 antibody levels and the risk of mother-child transmission.…”

“…In such countries, heterosexual HHV-8 contamination is relatively infrequent, but it is reported in women with the same risk factors (6 -8). In contrast, in HHV-8 endemic countries (Mediterranean basin, Africa, South America), most individuals get infected during childhood, because HHV-8 seroprevalence increases markedly from 1 to 15 years old to reach rates close to those observed in adults [e.g., 15% in French Guiana (9), 48% in Cameroon (10), 50% in Uganda (11), 58% in Egypt (12), and 70% in Tanzania (13)]. …”