HLA polymorphisms and detection of kaposi sarcoma-associated herpesvirus DNA in saliva and peripheral blood among children and their mothers in the uganda sickle cell anemia KSHV Study.

Kaposi sarcoma-associated herpesvirus (KSHV, also called Human herpesvirus 8 or HHV8) is a γ-2 herpesvirus that causes Kaposi sarcoma. KSHV seroprevalence rates vary geographically with variable rates recorded in different sub Sahara African countries, suggesting that effects of genetic and/or environmental factors may influence the risk of infection. One study conducted in South Africa, where KSHV seroprevalence is relatively low, found that carriage of human leukocyte antigen (HLA) alleles HLA-A*6801, HLA-A*30, HLA-A*4301, and HLA-DRB1*04 was associated with increased shedding of KSHV DNA in saliva. Confirmation of those results would strengthen the hypothesis that genetic factors may influence KSHV distribution by modulating KSHV shedding in saliva. To explore these associations in another setting, we used high resolution HLA-A, B, and DRB1 typing on residual samples from the Uganda Sickle Cell Anemia KSHV study, conducted in a high KSHV seroprevalence region, to investigate associations between HLA and KSHV shedding in saliva or peripheral blood among 233 children and their mothers. HLA-A and HLA-DRB1 alleles were not associated with KSHV shedding in our study, but our study was small and was not adequately powered to exclude small associations. In exploratory analyses, we found marginal association of KSHV DNA shedding in saliva but not in peripheral blood among children carrying HLA- B*4415 and marginal association of KSHV DNA shedding in peripheral blood but not in saliva among children carrying HLA- B*0801 alleles. The contribution of individual HLA polymorphisms to KSHV shedding is important but it may vary in different populations. Larger population-based studies are needed to estimate the magnitude and direction of association of HLA with KSHV shedding and viral control.

Molecular evidence for mother-to-child transmission of Kaposi sarcoma-associated herpesvirus in Uganda and K1 gene evolution within the host.

BACKGROUND: Epidemiological studies of Kaposi sarcoma (KS)-related herpesvirus (KSHV) indicate that having a KSHV-seropositive mother is a risk factor for KSHV infection in children. METHODS: We determined the KSHV K1 sequences in concordantly polymerase chain reaction-positive Ugandan mother-child pairs, to ascertain whether they shared the same viral strain. We also examined sequences amplified from saliva and buffy coat samples from the same subjects, to investigate potential intrasubject sequence differences. RESULTS: We obtained K1 sequences from 6 of 10 mother-child pairs. In 1 pair, the subtypes differed between mother and child. The mother and child in 2 other pairs shared the same subtype, but the sequences differed. The mother and child in 2 pairs shared KSHV strains with exact (100%) nucleotide homology. The last pair showed evidence of viral strain concordance between mother and child but also showed evidence of evolution of the viral sequence within the child. Of 26 study subjects, 19 showed no evidence of intrasubject K1 sequence variability, but, in 7 subjects, all of whom were children, amino acid variation of 1%-4% was observed. CONCLUSIONS: Our findings are consistent with KSHV transmission from maternal and nonmaternal sources in KS-endemic regions. Our results also provide evidence for ongoing evolution of the K1 gene in KSHV-infected children.

High levels of Epstein-Barr virus DNA in saliva and peripheral blood from Ugandan mother-child pairs.

In Africa, Epstein-Barr virus (EBV) is associated with Burkitt lymphoma. We measured levels of EBV DNA in saliva and buffy coats from 233 asymptomatic Ugandan children with sickle cell disease and their mothers by quantitative real-time polymerase chain reaction. EBV DNA was detected in saliva from 90% of the children (median [interquartile range [IQR]] level, 5.2 [4.2-6.0] log(10) copies/mL of saliva) and 79% of the mothers (median [IQR] level, 4.8 [3.7-5.6] log(10) copies/mL of saliva) (P < .001). EBV DNA was detected in buffy coats from 86% of the children (median [IQR] level, 2.5 [2.2-2.9] log(10) copies/1 x 10(6) peripheral white blood cells [PWBCs]) and 72% of the mothers (median [IQR] level, 2.7 [2.4-3.1] log(10) copies/1 x 10(6) PWBCs) (P = .24). Detection of EBV DNA in saliva was positively correlated with detection in buffy coats. EBV DNA was detected more frequently in saliva and buffy coats than was human herpesvirus 8 DNA. Our results indicate that EBV infection persists, with virus readily detectable in saliva and buffy coats from persons without apparent symptoms in Africa.

Water, socioeconomic factors, and human herpesvirus 8 infection in Ugandan children and their mothers.

BACKGROUND: Human herpesvirus 8 (HHV-8) infection is common in sub-Saharan Africa, but its distribution is uneven. Transmission occurs during childhood within families by unclear routes. METHODS: We evaluated 600 Ugandan children with sickle cell disease and their mothers for factors associated with HHV-8 seropositivity in a cross-sectional study. HHV-8 serostatus was determined using an HHV-8 K8.1 glycoprotein enzyme immunoassay. Odds ratios for seropositivity were estimated using logistic regression, and factor analysis was used to identify clustering among socioeconomic variables. RESULTS: One hundred seventeen (21%) of 561 children and 166 (34%) of 485 mothers with definite HHV-8 serostatus were seropositive. For children, seropositivity was associated with age, mother's HHV-8 serostatus (especially for children aged 6 years or younger), lower maternal education level, mother's income, and low-status father's occupation (P < 0.05 for all). Using communal standpipe or using surface water sources were both associated with seropositivity (OR 2.70, 95% CI 0.80-9.06 and 4.02, 95% CI 1.18-13.7, respectively) as compared to using private tap water. These associations remained, albeit attenuated, after adjusting for maternal education and child's age (P = 0.08). In factor analysis, low scores on environmental and family factors, which captured household and parental characteristics, respectively, were positively associated with seropositivity (P(trend) < 0.05 for both). For mothers, HHV-8 seropositivity was significantly associated with water source and maternal income. CONCLUSIONS: HHV-8 infection in Ugandan children was associated with lower socioeconomic status and using surface water. Households with limited access to water may have less hygienic practices that increase risk for HHV-8 infection.

Detection of kaposi sarcoma-associated herpesvirus DNA in saliva and buffy-coat samples from children with sickle cell disease in Uganda.

Among 233 children, Kaposi sarcoma-associated herpesvirus (KSHV) DNA was detected in 43% of children seropositive for both K8.1 and orf73, in 29% of children seropositive for K8.1 only, in 14% of children seropositive for orf73 only, and in 7% of children seronegative for both K8.1 and orf73; among 228 mothers, KSHV DNA was detected in 27%, 25%, 4%, and 1%, respectively. KSHV DNA was detected more frequently and at higher levels in saliva than in buffy-coat samples and in children than in mothers. In both children and mothers, detection in saliva was associated with detection in peripheral blood. Detection was associated with K8.1 seropositivity, younger age, and high household density, indicating the importance of in-household person-to-person transmission, likely via saliva.

Human herpesvirus 8 infection and transfusion history in children with sickle-cell disease in Uganda.

BACKGROUND: Although human herpesvirus 8 (HHV-8), the etiologic agent for Kaposi's sarcoma, can be detected in peripheral blood, blood-borne transmission of this virus has not been demonstrated. We studied the association between HHV-8 seropositivity and transfusion history among children with sickle-cell disease in Uganda, where HHV-8 infection is common in blood donors. METHODS: We studied 600 children (aged 0-16 years) with sickle-cell disease at Mulago Hospital, Kampala, from November 2001 through April 2002. By design, about half had previously been transfused. HHV-8 serostatus was determined using enzyme-linked immunosorbent assays for antibodies against HHV-8 proteins K8.1 and orf 73. We used logistic regression to test for an association between HHV-8 serostatus and transfusion history and a Markov model to estimate the transmission risk per transfusion and the cumulative risk from community (i.e., nontransfusion) sources. Statistical tests were two-sided. RESULTS: HHV-8 antibodies were detected in 117 of 561 (21%) children with unambiguous K8.1 results. HHV-8 seroprevalence among the never-transfused children increased with age from 7% in children aged 0-2 years to 32% in those aged 13-16 years (P(trend)<.001). HHV-8 seropositivity was more frequent in transfused than never-transfused children (24% versus 17%, odds ratio = 1.48, 95% confidence interval [CI] = 0.97 to 2.26; P =.07). Seropositivity increased with number of reported transfusions, with age-adjusted odds ratios of 0.97 (95% CI = 0.54 to 1.75), 1.13 (95% CI = 0.59 to 2.17), 1.76 (95% CI = 0.81 to 3.83), and 2.17 (95% CI = 1.18 to 3.99) for children with one, two, three, or four or more transfusions, respectively (P(trend) =.007). Overall, the estimated HHV-8 transmission risk was 2.6% per transfusion (95% CI = 1.9% to 3.3%), whereas the annual risk of infection unrelated to transfusion was 2.7% (95% CI = 1.7% to 3.7%). CONCLUSION: Our study suggests that blood transfusion is associated with a small risk of HHV-8 transmission. In Uganda, this risk is approximately equivalent to the 1-year cumulative risk of infection from community sources.