Congenital infection

Congenital infection with HHV6 could result from maternal infection acquired through transplantation or by inheritance via parental transmission of chromosomally integrated HHV6. Intrauterine transmission of HHV6 has recently been documented to occur in about 1% of children in a large and several smaller studies of normal newborns (Adams et al., 1998; Dahl et al., 1999; Daibata and Miyoshi, 1999; Hall et al., 2004). Intrauterine transmission had been suggested in a few cases by HHV6 DNA detection in fetuses and placentas, as well as cord blood (Ando et al., 1992; Aubin et al., 1992; Leach et al., 1994; Maeda et al., 1997a; Adams et al., 1998; Daibata et al., 1999; Ashshi et al., 2000; Baillargeon et al., 2000; Ohashi et al., 2002). The detection rate of HHV6 DNA in cord blood has ranged from 0 to 1.6% in studies examining 58-305 cord blood (Adams et al., 1998; Dahl et al., 1999; Daibata et al., 1999). In a study examining 5638 cord blood, the rate was 1% of live births, similar to that for cytomegalovirus (Fowler et al., 2003). The importance of this mode of transmission in terms of clinical and neurodevelopmental outcome is currently unknown. These congenitally infected infants appeared normal at birth, although the HHV6 DNA tended to persist in their peripheral blood mononuclear cells (Hall et al., 2004).

Transmission of HHV6 by integration of the virus DNA into human chromosomes has also been reported (Daibata et al., 1998; Luppi et al., 1998; Daibata et al., 1999; Hermouet and Minvielle, 2000; Tanaka-Taya et al., 2004). In Japanese subjects, the rate of detection of chromosomally integrated HHV6 has been reported as 0.2% (Tanaka-Taya et al., 2004). However, it is unclear whether the detection of the integrated HHV6 genome is truly inherited (Luppi et al., 1998; Hermouet et al., 2000).

Transmission to the infant via breast milk does not appear to occur, although studies on this are limited (Dunne and Jevon, 1993). Although HHV6 has been detected in the cervix and genital secretions of women, thus far sexual transmission has not been proven (Leach et al., 1994; Okuno et al., 1995; Maeda et al., 1997b).

Another documented mode of transmission is that from donated bone marrow containing HHV6, which caused a primary HHV6 infection in the bone marrow transplant recipient (Suga et al., 1998). Transmission of new HHV6 infection by transfusion or transplantation potentially could occur despite the recipient having had past HHV6 infection and possessing specific antibody. This raises the possibility that HHV6, which is latent in bone marrow progenitor cells, could be transmitted to recipients of blood transfusions or to those receiving other organs (Ward et al., 1989; Suga et al., 1998).

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