Abstract
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 log10 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.
Highlights
Human herpesvirus-6 (HHV-6) infects the vast majority of humans within the first few years of life, and febrile illness associated with primary infection is a major cause of health care visits for young children [1,2,3]
Primary Human herpesvirus 6 (HHV-6) infections were observed in 24 of the 31 at-risk infants during the study
All infections were typed as HHV-6B and 1 was a co-infection with HHV-6B
Summary
Human herpesvirus-6 (HHV-6) infects the vast majority of humans within the first few years of life, and febrile illness (roseola) associated with primary infection is a major cause of health care visits for young children [1,2,3]. Like other HHVs, HHV-6 establishes latency following primary infection and is persists within the host for life, with intermittent reactivation resulting in the shedding of infectious virus in saliva [7]. Cytomegalovirus (CMV) is widespread globally and commonly infects young children, in the developing world [8,9,10]. CMV is a major cause of illness following organ and stem cell transplantation and during untreated HIV infection [11,12,13,14]. CMV appears to be associated with immune senescence in the elderly, though the long-term consequences of infection are still being determined [15,16,17,18,19]
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