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Lack of Age Dependence in KSHV Seroprevalence among Children in a Population-based Study in South Africa: Evidence for at Least 2 Epidemiologic Patterns of KSHV Transmission in Africa
Lisa Butler*1, A Mosam2, P Kiepiela2, G Mbisa3, D Whitby3, C Brander4, D Scadden4, S Dollard5, and J Martin1
1Univ of California, San Francisco, US; 2Univ of KwaZulu Natal, Durban, South Africa; 3NCI-Frederick, MD, US; 4AIDS Malignancy Consortium, Baltimore, MD, US; and 5CDC, Atlanta, GA, US
Background: It has been established that Kaposi's
sarcoma-associated herpesvirus (KSHV) infection is
endemic among most African adult populations. The prevailing view is that a
single mode of KSHV spread—horizontal transmission in childhood—is primarily responsible
for endemic infection throughout the continent. However, few studies have
directly examined children, particularly in population-based samples in areas
where the endemic form (non-HIV-related) of Kaposi’s sarcoma is uncommon.
Methods: To study a region where endemic Kaposi’s
sarcoma is uncommon, we obtained a door-to-door sample of children ages 2, 4,
or 8 years, and their female caregiver, in the KwaZulu-Natal
region of South Africa.
As a comparison group where endemic Kaposi’s sarcoma is common, children younger
than age 10 were sampled at Mulago
Hospital in Kampala, Uganda.
Plasma was tested for KSHV antibodies with 2
enzyme immunoassays (using K8.1 andORF65 peptides) and an immunofluorescence
assay using induced BCBL-1 cells, all performed at the Centers for Disease Control
and Prevention. South African samples were also tested
by ORFK8.1 and ORF73 enzyme immunoassays at the National Cancer Institute.
Results: A total of 452 South African children (159 2-year-olds,
153 4-year-olds, and 140 8-year-olds) were evaluated. Overall KSHV seroprevalence was 6.4%, which did not differ by age among
all children (6.3%, 6.5%, and 6.4% in the 3 age groups, respectively; p = 0.96 for trend) or separately among
urban or rural children. Lack of age dependence was replicated with KSHV
testing at NCI. Among the children’s caregivers, KSHV seroprevalence
was 18%. In contrast, in 1291 Ugandan children, seroprevalence
among 2-year-olds (10%) was already nearly 50% higher than that of South
African 8-year-olds and increased with age: 16% at 4 years and 27% at 8 years old (p = 0.01 for trend).
Conclusions: In a contemporary population-based sample in South Africa—where
the endemic form of Kaposi’s sarcoma is uncommon—there is lack of age
dependence and low overall seroprevalence of KSHV
infection among children, suggesting little ongoing horizontal KSHV
transmission in childhood. Higher KSHV seroprevalence
is only seen in adults. This differs from Uganda where seroprevalence
is 10% by age 2 and further increases in childhood. The findings indicate at
least 2 patterns of KSHV transmission exist in Africa,
which, at least preliminarily, track with underlying incidence of endemic Kaposi’s
sarcoma. Whether KSHV infection in childhood is a critical determinant for Kaposi’s
sarcoma development as an adult, and is in part responsible for the high
incidence of endemic Kaposi’s sarcoma seen in areas like Uganda, merits
further investigation.
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