Early acquisition of herpes simplex virus type 1 antibodies in children—A longitudinal serological study
Introduction
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are closely related, ubiquitous α-herpesviruses. The most common clinical presentation of an HSV-infection is recurrent oral or genital lesions, but it can also cause, e.g. meningitis, encephalitis or severe neonatal infection. However, the majority of infected humans are silent carriers of HSV and the main factors in viral transmission are asymptomatic viral shedding or unrecognized HSV-infection (Mertz et al., 1992). The most common way to verify the presence of HSV in asymptomatic carriers or between symptomatic recurrences is serological analysis of HSV-antibodies.
HSV-1 is commonly acquired in childhood, by close contact to HSV-1 infected individuals, and a gradual development of HSV-1 antibodies is seen throughout childhood as estimated by point prevalence-studies (Smith and Robinson, 2002, Tunback et al., 2003). Herpes simplex virus type 2 (HSV-2) infections are primarily restricted to the genitoanal area and HSV-2 antibodies generally appear after sexual debut. However, also HSV-1 is now being increasingly recognized as a cause of genital infection (Lowhagen et al., 2000, Ross et al., 1993). Other human herpesviruses have been more extensively studied and in a study of human herpesvirus 6 (HHV-6) it was shown that the incidence of primary HHV-6 infection mainly occurred at the age of 9–21 months, with an incidence of 40% by the age of 12 months and 77% at 24 months (Zerr et al., 2005). Cytomegalovirus infection, on the other hand, can be acquired congenitally but transmission by breast-milk is also well established (Schleiss and McVoy, 2004).
In this investigation a longitudinal analysis of series of blood samples collected from mother and child was made, offering a possibility of establishing the time for acquisition of HSV in the child, as well as the disappearance of maternal HSV-1 and HSV-2 antibodies. The results showed that a majority of new HSV-1 infections occurred early, suggesting that a main period for HSV-1 transmission is during infancy rather than during the years in school.
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Study population
Blood samples from healthy term infants were collected at the age of 3, 5, 6, 12, 13 and 30 months of age in 1990–1993, to determine antibodies against Haemophilus influenzae type b and tetanus toxoid, after vaccination with two different H. influenzae type b conjugate vaccines (Carlsson et al., 1994, Carlsson et al., 1996). A sample from respective mother was collected when the infant was 3-month old. Approval from the Ethics Committee of the Medical Faculty of Göteborg University was given in
HSV-1
In the 129 series tested, 84 of the maternal serum samples were positive, giving an HSV-1 seroprevalence of 65%. Detectable HSV-1 antibodies in their 3-month-old children were seen in 68% (57/84), whereas no child with an HSV-1 negative mother had measurable antibodies at that age (Fig. 1). The geometric mean titer of HSV-1 antibodies in mothers whose children had detectable HSV-1 antibodies was 1239 and the titer for those whose children were seronegative, was 272 (p = 0.0001). The number of
Discussion
This study demonstrates that seroconversion to HSV-1 commonly occurs already during infancy and we found an estimated HSV-1 seroprevalence of 17% at the age of 12 months. A majority of new infections was seen within the first 13 months of life, with an incidence of two new infections per month during the second half of infancy compared to <1 per month after 13 months of age. Since children in Sweden rarely attend to daycare centers before the age of one, our data indicate that most children
Acknowledgements
We thank Zoreh Sadegsadeh for excellent technical assistance. This work was supported by grants from The Medical Society of Göteborg, The LUA Foundation at Sahlgrenska University Hospital and The Swedish Research Council (grant no 11225).
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