Estimating the Risk of Human Herpesvirus 6 and Cytomegalovirus Transmission to Ugandan Infants from Viral Shedding in Saliva by Household Contacts

Human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) infections are common in early childhood. In a prospective Ugandan birth cohort study, most infants acquired HHV-6 (24/31; 77%) and CMV (20/30; 67%) during follow-up. To assess the transmission risk, we modeled a dose-response relationship between infant HHV-6 and CMV infections and weekly oral viral shedding by mothers and all other (secondary) children in the home. Oral viral loads that were shed by mothers and secondary children were significantly associated with HHV-6 but not CMV transmission. While secondary children had higher and more frequent HHV-6 shedding than their mothers, they had a lower per-exposure transmission risk, suggesting that transmission to maternal contacts may be more efficient. HHV-6 transmission was relatively inefficient, occurring after <25% of all weekly exposures. Although HHV-6 transmission often occurs following repeated, low dose exposures, we found a non-linear dose-response relationship in which infection risk markedly increases when exposures reached a threshold of > 5 log(10) DNA copies/mL. The lack of association between oral CMV shedding and transmission is consistent with breastfeeding being the dominant route of infant infection for that virus. These affirm saliva as the route of HHV-6 transmission and provide benchmarks for developing strategies to reduce the risk of infection and its related morbidity.