Congenital HHV6 and HHV7 Infections

Abstract & Commentary

Synopsis: HHV6 DNA was detected in 57 of 5638 (1%) cord blood samples, while HHV7 DNA was detected in none of 2129 cord blood samples. Congenital HHV6 infections were clinically and virologically distinct from postnatal HHV6 infections.

Source: Hall CB, et al. Congenital Infections With Human Herpesvirus 6 (HHV6) and Human Herpesvirus 7 (HHV7). J Pediatr. 2004;145:472-477.

Using nested PCR capable of detecting < 10 genome copies in cord blood mononuclear cells, human herpesvirus 6 (HHV6) DNA was detected in 57 of 5638 (1%) cord blood samples, and human herpesvirus 7 (HHV7) DNA was detected in none of 2129 cord blood samples. Two-thirds (38) of the 57 congenital HHV6 infections were with variant B (HHV6B), and one-third (19) with variant A (HHV6A). HHV6 IgG antibody was present in the cord blood of all 57 infants with congenital infection, but the geometric mean antibody titer was significantly lower in these infants than in 57 matched infants without congenital HHV6 infection (8.79 vs 9.48 log2, P = 0.03). HHV7 IgG antibody was present in all of the cord bloods that were tested (> 6.32 log2). The replicative state of HHV6 could be determined by RT-PCR in 48 (16 HHV6A and 32 HHV6B) cord blood samples. Active viral replication was documented in 5 of 48 (10%) infants, all of which were infected with HHV6B.

Follow-up PCR of peripheral blood mononuclear cells within 2 years of birth (46 samples from 17 children) showed 42 (91%) with HHV6 DNA. By comparison, follow-up within 2 years of postnatal HHV6 infection acquired > 1 month of age (1919 samples from 1044 children) showed 1327 (69%) with HHV6 DNA (P = 0.03). Active viral replication, as documented by RT-PCR, over the subsequent 2 years was demonstrated in 2 of 22 (9%) samples from children with congenital infection and in 45 of 1323 (3.4%) samples from children with postnatal infection.

Comment by Hal B. Jenson, MD, FAAP

This study confirms the congenital infection rate reported by previous smaller studies, and is the first to study congenital HHV7 infection. It is surprising that no congenital HHV7 infection was detected because of the ubiquitous prevalence of both viruses and their virological similarity. In fact, HHV7 is shed more frequently in saliva (> 95%) of healthy adults, and, unlike HHV6, in 10% of breast milk samples. The divergence in HHV6 and HHV7 congenital infections is intriguing, given the genetic similarities of these viruses to each other and to cytomegalovirus (CMV).

This study shows interesting differences between congenital and postnatal HHV6 infections. Almost all postnatal HHV6 infections are caused by HHV6B, whereas one-third of congenital infections in this study were HHV6A. Congenital HHV6 infection was associated with a significantly greater frequency of detection of virus in peripheral blood mononuclear cells and a higher rate of active replication during the subsequent 2 years than with postnatal infection. However, most infants with congenital HHV6 infection did not show active HHV6 replication, which is very different from the high rates of CMV replication and shedding among infants with congenital CMV infection. In contrast to primary HHV6 infection that is often symptomatic, resulting in roseola, congenital HHV6 infection is asymptomatic, which may reflect the presence of maternal antibody in all cases. Congenital CMV infection is also usually asymptomatic at birth (90-95%), although infected infants are at increased risk for hearing loss and developmental deficits. It is unknown if infants with congenital HHV6 infection are at similar risk but this will be an important question to answer.

Hal B. Jenson, MD, FAAP, Chair, Department of Pediatrics, Director, Center for Pediatric Research, Eastern Virginia Medical School and Children’s Hospital of the King’s Daughters, Norfolk, VA, is Associate Editor for Infectious Disease Alert.