Human herpes virus-8 infection among pregnant women and their children: Results from the sardinia-IDDM study 2

Marked variations exist in the distribution of human herpesvirus 8 (HHV-8) infection in different geographical and socio-economic settings, mirroring variations in incidence rates of classic Kaposi's sarcoma (KS). Thus, HHV-8 infection is more frequent in Italy than in the United States1-3 and, within Italy, in Sardinia and Sicily, 2 regions with high incidence rates of classic KS, than in the northern part of the country, where classic KS is less frequent.3-6 In Western countries, HHV-8 infection is usually acquired after adolescence (i.e., at the beginning of sexual activity), whereas in Africa it occurs commonly in childhood, with prevalence reaching relatively high levels before the age of sexual activity.7 This finding indicates that transmission modes other than sexual intercourse may be important for HHV-8 acquisition also in Western countries, possibly through vertical and/or horizontal transmission.8, 9 To assess the extent to which HHV-8 can be transmitted to children, we performed HHV-8 serological testing on 564 mother–infant paired (MIP) serum samples derived from cord blood and from children between 12 and 36 months of age. The study took advantage of a blood bank, implemented in Sardinia between 1993 and 1997, in the setting of a large population-based study aimed at investigating the causes of insulin-dependent diabetes.10 Blood samples were collected at delivery from the mother's cord blood and, later, from their children at the ages of 12, 24 and 36 months and tested for HHV-8 antibodies. Serum samples were stored at –20°C in laboratories at Tor Vergata University (Rome, Italy). As previously described,11 IgG antibodies to HHV-8 lytic antigens were detected using immunofluorescence assays based on the BCBL-1 cell line (obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH, from Drs. M. McGrath and D. Ganem). Samples reactive at >1:20 dilution in the IgG anti-lytic test were considered positive. The χ2 test or, when appropriate, Fisher's exact test or the χ2 test for trend was used to assess statistical differences in the proportion of HHV-8 seropositivity rates. The concordance of HHV-8 status for each MIP was determined using the K statistic.12 Thirty-three of the 564 umbilical cord blood samples (5.9%), and 18 of the 564 children (3.2%) were positive for anti-lytic HHV-8 antibodies (Table I). HHV-8 infection was approximately 4-fold higher among children born to HHV-8-positive mothers (12.1%) than in those born to HHV-8-negative mothers (2.6%) (p = 0.02), but the global concordance was low (K = 0.12). No statistically significant differences emerged when the analysis was separately conducted among children tested at 12 months of age (Fisher's exact test p = 0.10) or at 24 or 36 months of age (Fisher's exact test p = 0.06) (Table I). In children, HHV-8 seropositivity tended to increase with increasing HHV-8 antibody titer of the mother, but this observation was based only on 4 HHV-8-positive children (Table I). Detection of HHV-8 in cervicovaginal secretions, a rare event favored by concomitant inflammatory lesions of the genital tract, and in saliva13-15 supports the possibility that HHV-8 may be transmitted from mother to child and horizontally within the family. In endemic populations, these appear to be the prevailing modes of HHV-8 acquisition during childhood and adolescence.7-9 The findings of our MIP investigation conducted in Sardinia indicate that about 10% (95% confidence interval 6.4%–17.8%) of children born to HHV-8-seropositive mothers acquire HHV-8 infection. Overall, in our study, children born to HHV-8-positive mothers were more likely to be HHV-8-positive than those born to HHV-8-negative mothers; but because of the small number of infected mothers, our study did not offer the opportunity to fully investigate transmission patterns. For instance, the above-mentioned association was weaker when the MIP analysis was stratified according to age or by residence in high- or low-risk areas of Sardinia.16 Moreover, the overall MIP concordance was low. The presence of antibodies to HHV-8 in older children was assumed to strengthen the role played by horizontal transmission (possibly related to saliva droplets, as seen with other herpesvirus infections, e.g., Epstein-Barr virus).14 This hypothesis appears to be confirmed by our findings, though the detection of higher HHV-8 seroprevalence rates in older children was not statistically significant. Our results are somewhat consistent with those of a previous study, which used a different design, showing that, in Sardinia, prevalence rates of HHV-8 infection were similar in spouses and relatives of KS patients and suggesting the existence of non-sexual modes of HHV-8 transmission within adult family members.17 In conclusion, although based on a small number of HHV8-positive mothers, the results of our MIP study conducted in Sardinia appear to confirm that HHV-8 can be transmitted from mother to child also in Western countries. The actual role of non-sexual transmission in the spread of HHV-8 infection in children in Western countries needs to be better assessed by studies designed to monitor antibody dynamics from delivery to 24 months of age, possibly based on larger samples of HHV-8-positive mothers. Yours sincerely, We thank Dr. B. Ensoli and Dr. P. Monini for invaluable help in the development of serological testing; Ms. F. Farchi for data input and secretarial support; and Mr. J. Canwell for text editing. The work of the IDDM Study Group in Sardinia is supported by ASRIS (Cagliari) and ADCT (London). Diego Serraino*, Mattia Locatelli , Marco Songini , Rocco Cirillo§, Gian Franco Bottazzo , Massimo Andreoni¶, Silvia Franceschi**, Giovanni Rezza , * Centro di Riferimento AIDS e Servizio di Epidemiologia delle Malattie Infettive, IRCCS Lazzaro Spallanzani, Rome, Italy, Direzione Scientifica, IRCCS Ospedale del Bambino Gesù, Rome, Italy, Department of Internal Medicine, Ospedale San Michele, Cagliari, Italy, § Department of Medical Sciences, Center for Metabolic Diseases, Cagliari University, Cagliari, Italy, ¶ Infectious Disease Clinic, Tor Vergata University, Rome, Italy, ** Epidemiology Unit, IRCCS Centro di Riferimento Oncologico, Aviano, Italy, Centro Operativo AIDS, Istituto Superiore di Sanità, Rome, Italy