Risk Factors for Kaposi’s Sarcoma–Associated Herpesvirus DNA in Blood and in Saliva in Rural Uganda

Abstract

Background Detectable Kaposi’s sarcoma–associated herpesvirus (KSHV) DNA in blood and increased antibody titres may indicate KSHV reactivation, while the transmission of KSHV occurs via viral shedding in saliva. Methods We investigated the risk factors for KSHV DNA detection by real-time polymerase chain reaction in blood and by viral shedding in saliva, in 878 people aged 3 to 89 years of both sexes in a rural Ugandan population cohort. Helminths were detected using microscopy and the presence of malaria parasitaemia was identified using rapid diagnostic tests. Regression modelling was used for a statistical analysis. Results The KSHV viral load in blood did not correlate with the viral load in saliva, suggesting separate immunological controls within each compartment. The proportions of individuals with a detectable virus in blood were 23% among children aged 3–5 years and 22% among those 6–12 years, thereafter reducing with increasing age. The proportions of individuals with a detectable virus in saliva increased from 30% in children aged 3–5 years to 45% in those aged 6–12 years, and decreased subsequently with increasing age. Overall, 29% of males shed in saliva, compared to 19% of females (P = .008). Conclusions Together, these data suggest that young males may be responsible for much of the onward transmission of KSHV. Individuals with a current malaria infection had higher levels of viral DNA in their blood (P = .031), compared to uninfected individuals. This suggests that malaria may lead to KSHV reactivation, thereby increasing the transmission and pathogenicity of the virus.

Kaposi’s sarcoma-associated herpesvirus T cell responses in HIV seronegative individuals from rural Uganda

“…3). As previously reported 26 , anti-K8.1 IgG antibody levels are higher in those with detectable KSHV DNA in PBMC (Fig. 5b) while no difference is observed with anti-ORF73 antibody levels (Fig.…”

“…For this study, we recruited individuals from the GPC who were KSHV seropositive, but HIV seronegative in 2017, to investigate determinants of KSHV viral detection. Only one individual was recruited per household 26 . Blood samples were processed to isolate PBMC (stored in liquid nitrogen for later immunological assays) and plasma (stored at −80 °C for later use).…”

“…Detection of KSHV DNA as well as its quantity in peripheral blood mononuclear cells (PBMC) has been associated with KS disease progression [21][22][23][24] and increased HIV viremia in HIVinfected individuals 25 . In individuals without KS-or any other KSHV-associated disease, we have previously shown that KSHV DNA in PBMC was associated with increased KSHV antibody levels to lytic KSHV protein K8.1 and to malaria parasitaemia 26 . An association between increased lytic KSHV antibody levels and KS disease risk has also been reported 27 .…”

Variation in KSHV prevalence between geographically proximate locations in Uganda

“…Several risk factors for KSHV have been identified by our group, and others, including infection with HIV, malaria and helminths [2,3,[6][7][8][9][10][11]. The distribution of these may vary between regions within the same country leading to differences in the spread of KSHV, even between geographically proximate locations.…”

Malaria during pregnancy and transplacental transfer of Kaposi sarcoma-associated herpesvirus (KSHV) antibodies: a cohort study of Kenyan mother and child pairs

“…Malaria has been previously associated with KSHV infection and non-bed net use with KS disease in sub-Saharan Africa [2,[21][22][23][24][25][26]. We hypothesized that one of the mechanisms driving the association between malaria and KSHV infection in sub-Saharan Africa was through in utero malaria exposure that altered transplacental transfer of maternal IgG; the neonates first line of defense against infection.…”