Multilane highway to congenital infection.

Received 15 May 2007; accepted 15 May 2007; electronically published 1 October 2007. Potential conflicts of interest: P.E.P. receives royalties for sales of a reagent that can be used to diagnose HHV-6 infections. J.G. declares no potential conflicts. Financial support: Cleveland Clinic. Reprints or correspondence: Dr. Philip E. Pellett, Cleveland Clinic, 9500 Euclid Ave., NN10, Cleveland, OH 44195 (pelletp @ccf.org). The Journal of Infectious Diseases 2007;196:1276–8 2007 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2007/19609-0002$15.00 DOI: 10.1086/522434 Congenital infections are an important clinical and societal problem that can be devastating for children and their families. Although many congenital infections are asymptomatic, some are associated with overwhelming consequences requiring long-term support that can include physical care and addressing learning and other developmental difficulties. Advances in medical care have allowed identification and prevention or treatment of some congenital infections. For example, primary maternal syphilis is likely to cause fetal death, and latent maternal syphilis may result in no fetal or neonatal disease or in an easily missed latent infection that ultimately causes devastating disease if not treated. Universal screening and treatment of pregnant women for syphilis has almost completely eradicated congenital disease. Likewise, antiviral interruption of mother-to-fetus transmission of HIV has almost completely eliminated congenital HIV infection in many countries. These are remarkable demonstrations of the value of attending to congenital infections. One of the most important congenital infections in the United States is cytomegalovirus (CMV) infection. As discussed recently in these pages [1, 2], congenital CMV infections can lead to significant learning disabilities and cause a significant portion of cases of early childhood sensorineural hearing loss. The latter problem is particularly vexing because hearing loss associated with congenital CMV infection may not develop for months or years, thus escaping detection by standard neonatal hearing tests. Screening and treatment programs for congenital CMV infections are in evaluation internationally. CMV is a member of the betaherpesvirus subfamily (the Betaherpesvirinae). The other human betaherpesviruses, human herpesvirus (HHV)–6 and HHV-7, share a number of biological properties with CMV, including lymphotropism and a propensity to infect children [3]. Two major forms of HHV-6 have been identified, variants A and B. The clinical spectrum of HHV-6A remains to be defined. HHV-6B is highly prevalent, causes most cases of the early childhood disease roseola (exanthem subitum or sixth disease), and has been associated with diverse diseases in immunocompromised patients. Approximately 20% of children from 6 to 12 months old who are admitted to emergency departments with febrile illnesses are experiencing primary HHV-6B infections. Primary infections with HHV-7 cause a small percentage of roseola cases and have been associated with febrile convulsions at a rate higher than that for HHV-6. Congenital transmission of HHV7 has not been detected. Approximately 1% of children are congenitally infected with HHV-6, a frequency similar to that for CMV [4]. Fifty-seven occurrences of congenital infection were detected among the 15600 children examined; all were asymptomatic. For perspective, this sample size would not have allowed reliable detection of a symptomatic case of CMV infection (∼1% of children congenitally infected with CMV are symptomatic). Thus, the contribution of HHV-6 to congenital disease remains to be determined, and the modes of transmission have not been fully defined. In this issue of the Journal, Caserta et al. [5] describe a large-scale study to examine the prevalence of HHV-6 and HHV-7 nucleic acids in blood samples and cervical swabs from pregnant women, to detect possible associations with congenital transmission of these viruses. Their article is the most recent chapter in an ongoing study of the natural history of pediatric HHV-6 and HHV-7 infections by Dr. Caserta, Dr. Hall, and associates. This work has proven to be valuable in its illumination of the spectrum of disease associated with these viruses and in understanding enough of their habits to make