The objectives of the work are to elucidate the incidence and virological findings of chromosomally integrated human herpesvirus 6 (ciHHV-6) in Japanese population and to analyze an association between ciHHV-6 and the clinical manifestation of exanthema subitum (ES). Real-time polymerase chain reaction was performed to determine HHV-6 DNA loads in 2347 cord blood samples from healthy neonates (cohort A), febrile children less than 5 years old (cohort B), and hematopoietic cell transplant recipients (cohort C). CiHHV-6 was confirmed by detection of high copy numbers of viral DNA in somatic cells. The integration site was determined by fluorescent in situ hybridization analysis. In the ciHHV-6 subjects of cohorts A and B, HHV-6 antibody titers were measured, the history of ES was obtained, and the incidence of ES was compared with non-ciHHV-6 children without primary HHV-6B infection in the cohort B. CiHHV-6 was detected in 14 (0.60%) of the 2347 samples: A (6/1006, 0.60%), B (6/790, 0.76%), and C (2/551, 0.36%). The integration sites were on chromosome 22q in seven cases, Yp in two cases, and 17q and Xp in one case. No past history of ES was observed in 11 of the 12 subjects. Nine children with ciHHV-6 underwent serological analysis and were found to be positive for HHV-6 IgG antibodies. Incidence of ES was statistically higher in the control subjects than the ciHHV-6 subjects (P = 0.0039). In Japan, the frequency of ciHHV-6 was 0.60%. A high incidence of ciHHV-6A, specifically in chromosome 22, is a characteristic finding among the Japanese. CiHHV-6 may interfere with the clinical symptoms of primary HHV-6B infection.

Background Human herpesvirus 6 (HHV-6) can be genetically transmitted from parent to child as inherited chromosomally integrated HHV-6 (iciHHV-6). HHV-6 reactivation occurs in pregnant women with iciHHV-6. We showed no gender differences in the frequency of index cases with iciHHV-6 but inheritance from the father was more common. We evaluated the association between iciHHV-6 status and spontaneous abortion. Methods iciHHV-6 was confirmed by high viral DNA copy numbers in whole blood and somatic cells. The origin of integrated viral genome, paternal or maternal, was examined using the same method. The pregnancy history of 23 mothers in families with iciHHV-6 and 285 mothers in families without iciHHV-6 was abstracted. Results Of 23 iciHHV-6 index cases, eight mothers and 15 fathers had iciHHV-6. Spontaneous abortion rates in mothers with and mothers without/fathers with iciHHV-6 and mothers in families without iciHHV-6 were 27.6%, 10.3%, and 14.8%, respectively (p = 0.012). Mother with iciHHV-6 (OR 6.41, 95%CI 1.10–37.4) and maternal age at the most recent pregnancy ≥40 years (OR 3.91, 95%CI 1.30–11.8) are associated with two or more spontaneous abortions. Conclusion Mothers with iciHHV-6 is a risk factor for spontaneous abortion.

SUMMARY:In this study, we investigated the prevalence of antibodies against 9 viral species found in umbilical cord blood from 561 neonates in 2013. Serum IgG antibodies against the following viruses were measured: herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), measles virus (MV), rubella virus (RV), mumps virus (MuV), and human parvovirus B19 (HPV B19). A survey questionnaire regarding past medical history and maternal immunization status for the vaccine-preventable diseases of varicella, measles, rubella, and mumps was simultaneously administered. The results were compared with previous data collected in 2001-2002 from 378 umbilical cord blood samples. Viral seroprevalence data were: HSV, 54z; VZV, 96z; EBV, 96z; CMV, 67z; HHV-6, 100z; MV, 95z; RV, 94z; MuV, 64z; and HPV B19, 55z. The seroprevalence of CMV, MV, and MuV were significantly lower in 2013 than in 2001 -2002 MV, 98z; MuV, 93z). Compared with the 2001-2002 data, the mean IgG antibody values of the 4 vaccine-preventable diseases were significantly lower, and vaccination coverage for those diseases among mothers was significantly higher. Thus, attention should be paid to antibody levels in women of childbearing age in the future.

Objective: This cohort study, based on the design of a prior study in the United States, was conducted to elucidate the clinical features of primary human herpesvirus-6B (HHV-6B) infection. Methods: Between June 2014 and May 2016, febrile children younger than 5 years who visited the emergency room (ER) and underwent blood examination were enrolled in this study. Results: Fifty-nine (12%) of the 491 patients were diagnosed with primary HHV-6B infection. The rates of both simple and complex febrile seizure were significantly higher in patients with primary HHV-6B infection than in those without (P < 0.001 and P = 0.008, respectively). The median age at primary HHV-6B infection was 15 months. Forty-seven (79.7%) of the 59 patients with primary HHV-6B infection were younger than 2-year-old. Clinical features were compared between HHV-6B–infected patients older and younger than 2 years. The frequency of apparent infection (exanthema subitum) was significantly higher in the younger patients (P = 0.01). The median leukocyte (P = 0.01) and lymphocyte (P < 0.001) counts in the patients older than 2 years were significantly lower than those in the younger patients. Conclusions: Primary HHV-6B infection accounted for 12% of ER visits. Secondary febrile seizures, in particular the complex type, were considered to be a major contributor to the disease burden of primary HHV-6B infection. The timing of primary HHV-6B infection occurred at older ages than in past reports, and the frequency of inapparent infection was higher in older patients.

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