Age of Acquisition and Manifestations of HHV6 Infection
Abstract & Commentary
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
Synopsis: HHV6 infection occurred primarily during the first 2 years of life. Most infections were symptomatic, but with nonspecific symptoms. Among 81 children with well-defined time of infection, roseola occurred in only 23%. None of these children had febrile seizures.
Source: Zerr DM, et al. A Population-Based Study of Primary Human Herpesvirus 6 Infection. N Engl J Med. 2005; 352:768-776.
A prospective, population-based study in Seattle, Washington, of the acquisition of human herpesvirus 6 (HHV6) was conducted among 277 children from birth through the first 2 years of life by quantitatively testing saliva weekly for HHV6 DNA by PCR. Primary infection was documented in 130 children, with cumulative incidence of 40% by 12 months of age and 77% by 24 months of age. The peak age of acquisition was from 9-21 months. In 3 infants, HHV6 DNA was detected in some during the first week of life, which suggests in utero or perinatal infection. HHV6 acquisition was associated with female sex (adjusted hazard ratio, 1.7: 95% CI, 1.2-2.4) and having older siblings (adjusted hazard ratio, 2.1: 95% CI, 1.4-2.9). Breastfeeding and childcare did not appear to influence acquisition of HHV6.
Among the 81 children with a well-defined time of acquisition of HHV6, 93% had symptoms. Fussiness (69%), rhinorrhea (65%), and fever (57%) were the most common symptoms. Rash occurred in 31%, and none had seizures. Roseola occurred in only 19 of the 81 children (23%). Of these 19 children with roseola, the onset of clinical symptoms was within 1 week in 11 (58%), from 1-2 weeks in 6 (32%), and from 2-3 weeks in 2 (11%). Almost 40% of the children visited a physician for evaluation of HHV6-related symptoms. The mean duration of symptoms was 9 days, including fever that lasted a median of 3 days.
Salivary HHV6 shedding was initially at low levels following onset of symptoms (median, 1700 copies/mL), but the levels tended to rise over several weeks and reach a peak at 8-12 weeks (100,000-130,000 copies/mL) and then decrease to a stable plateau over time (40,000 copies/mL).
Comment by Hal B. Jenson, MD, FAAP
Most epidemiological studies of HHV6 have used serology for diagnosis, which does not date the time of infection as precisely as testing for HHV6 DNA by PCR. Serologic studies are especially problematic in infants because of the presence of maternal antibodies. These elegantly designed, population-based studies included quantitatively measurement of salivary HHV6 excretion weekly. The results showed a high level of HHV6 acquisition during the first 2 years of life. More importantly, they showed that most children with primary HHV6 infection are symptomatic but have non-specific symptoms, such as fussiness. The classical syndrome of roseola occurred in only 23% of children, confirming the belief that most HHV6 infection is clinically indistinguishable from other viral infections of childhood. Nevertheless, almost 40% of HHV6 infections resulted in a visit to a physician.
Many studies have reported the association of primary HHV6 infection with seizures, but this may reflect the bias of using an uncommon outcome as a study entry criterion. Febrile seizures appear to be infrequently associated with primary HHV6 infection.
These studies also documented prolonged oral shedding of HHV6 at high titers, similar to the oral shedding of Epstein-Barr virus. The impact of this on the epidemiology of HHV6 is clearly evident, as having older siblings is a significant risk factor for infection. It also confirms that HHV6 shedding is ubiquitous, and should be presumed for a majority of children at 2 years of age.
HHV6 infection occurred primarily during the first 2 years of life. Most infections were symptomatic, but with nonspecific symptoms. Among 81 children with well-defined time of infection, roseola occurred in only 23%. None of these children had febrile seizures.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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