Temporal patterns of asymptomatic SARS-CoV-2 infection among pediatric population in Japan: A 3-year analysis.

To elucidate the seroprevalence and rate of asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Japanese children, serological analysis was performed using serum samples collected from March 2020 to February 2023. A total of 1493 serum samples were collected during the first study period (March 2020 to February 2021). None of the serum samples was positive for SARS-CoV-2 antibody. In the second period (March 2021 to February 2022), seven of the 1055 patients (0.7%) experienced SARS-CoV-2 infection. The third period (March 2022 to February 2023) was divided into three terms: from March to June 30, 2022; from July to October 2022; and from November 2022 to February 2023. The seroprevalence gradually increased throughout this period, with rates of 6.0%, 18.6%, and 30.4% in the three terms, respectively. Pediatric cases of asymptomatic SARS-CoV-2 infection occurred after the surge of Omicron variants. Since none of the SARS-CoV-2 antibody-positive patients had a previous history of coronavirus disease 2019, the seroprevalence rate in this study may represent the rate of asymptomatic infection.

Serological analysis of severe acute respiratory syndrome coronavirus 2 infection in children with Kawasaki disease.

Multisystem inflammatory syndrome in children (MIS-C) was reported as a severe complication of coronavirus disease 2019; an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and was suggested to be associated with Kawasaki disease (KD) in terms of severe systemic inflammation and mucocutaneous symptoms. Because severe gastrointestinal symptoms and systemic shock are more frequently observed with MIS-C, patients with mild MIS-C might have been diagnosed with KD. In this study, titers of IgG antibodies against the SARS-CoV-2 S (S-IgG) and N proteins (N-IgG) were measured in 99 serum samples collected from patients with KD treated between January 2020 and December 2021 to evaluate the relationship between KD and SARS-CoV-2 infection. S-IgG were detected in only one patient out of 99 patients. This patient had coronavirus disease 2019 (COVID-19) 10 months before KD onset, and was unlikely MIS-C. According to characters of S-IgG and N-IgG, the patients was unlikely infected with SARS-CoV-2 just before the onset of KD. In addition to this study, the 26th Nationwide Survey and previous studies showed an association between KD and SARS-CoV-2 to be unlikely. In conclusion, SARS-CoV-2 infection was not observed in patients with KD until Delta predominance in Japan by the method of detecting SARS-CoV-2 IgG.

Changes in trends of pediatric ß- and γ-herpesvirus infections during the COVID-19 pandemic: A single-center observational study.

Nonpharmaceutical interventions (NPIs) to control COVID-19 have decreased the incidence of many pediatric infectious diseases. The epidemiology of ß- and γ-herpesvirus infections might have been affected by NPIs. The aim of this study was to elucidate changes in trends in ß- and γ-herpesvirus infections and complex febrile seizures (cFS) of viral etiology before and during the COVID-19 pandemic. Between April 2017 and March 2021, febrile children aged ≤5 years were enrolled. Detection of EBV, CMV, HHV-6B, and HHV-7 DNA in serum was performed using real-time PCR. The epidemiology of viral infections and cFS were compared between the prepandemic and pandemic periods. During the observation period, 1432 serum samples were collected. The mean number of febrile children decreased during the pandemic period, but the number of patients with HHV-6B infection increased from 35 (9.3% of all febrile children) per year before the pandemic to 43 (15.5%) during the pandemic. The change in the proportion of patients with primary HHV-6B infection was 6.50% (95% confidence interval [CI], 2.05%-11.3%; p = 0.0047). The mean number of patients with cFS decreased during the pandemic period, but the number of patients with HHV-6B-associated cFS was stable throughout the observation period. Therefore, the change in proportion of patients with cFS caused by primary HHV-6B infection was 49.5% (95% CI, 12.2%-60.5%; p = 0.0048). The disease burden of primary HHV-6B infection among patients in the emergency room remained unchanged, with a significant increase in the relative proportion after the COVID-19 pandemic began.

Analysis of the reliability of rapid diagnostic tests for varicella, including breakthrough cases.

In the era of universal varicella vaccination, diagnosis of varicella is challenging, especially for breakthrough cases. We sought to clarify the reliability of direct varicella-zoster virus (VZV) loop-mediated isothermal amplification (LAMP) and DermaQuick® VZV using the immunochromatography technique as rapid diagnostic tests for varicella. In addition, the usefulness of saliva as a sample type for direct LAMP was investigated. Among the 46 enrolled patients with suspected VZV infection, 31 patients (67.3%) were positive for the nucleic acid test based on real-time PCR from skin swab samples. Direct LAMP of skin swabs was positive in 29 (63.0%) of 46 patients. DermaQuick® VZV was positive in 25 (54.3%) of 46 patients. VZV DNA was detected in only 48.4% of oral swabs with the direct LAMP method. With real-time polymerase chain reaction (PCR) as the standard for diagnosing varicella, the sensitivity and specificity of DermaQuick® VZV were 80.7% and 100%, respectively. The sensitivity and specificity of direct LAMP from skin swabs were 93.6% and 100%, respectively. The sensitivity and specificity of real-time PCR for DNA extracted from oral swabs were 74.2% and 93.3%, respectively. Thus, oral swab samples are not suitable for breakthrough varicella diagnosis. Although DermaQuick® VZV is considered the most convenient point-of-care test for varicella, its sensitivity and specificity were lower than those of direct VZV LAMP.

Inherited Chromosomally Integrated Human Herpesvirus 6 Is a Risk Factor for Spontaneous Abortion.

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 found no sex 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, 8 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 = .012). Mothers with iciHHV-6 (odds ratio [OR], 6.41; 95% confidence interval [CI], 1.10-37.4) and maternal age at the most recent pregnancy ≥40 years (OR, 3.91; 95% CI, 1.30-11.8) were associated with 2 or more spontaneous abortions. CONCLUSIONS: Mothers with iciHHV-6 is a risk factor for spontaneous abortion.

Molecular characterization of rotaviruses obtained from patients with rotavirus-associated encephalitis/encephalopathy.

Group A rotavirus (RVA) rarely causes severe complications such as encephalitis/encephalopathy. However, the pathophysiology of this specific complication remains unclear. Next-generation sequence analysis was used to compare the entire genome sequences of RVAs detected in patients with encephalitis/encephalopathy and gastroenteritis. This study enrolled eight patients with RVA encephalitis/encephalopathy and 10 with RVA gastroenteritis who were treated between February 2013 and July 2014. Viral RNAs were extracted from patients' stool, and whole-genome sequencing analysis was carried out to identify the specific gene mutations in RVA obtained from patients with severe neurological complications. Among the eight encephalitis/encephalopathy cases, six strains were DS-1-like G1P[8] and the remaining two were Wa-like G1P[8] (G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1). Meanwhile, eight of the 10 viruses detected in rotavirus gastroenteritis patients were DS-1-like G1P[8], and the remaining two were Wa-like G1P[8]. These strains were further characterized by conducting phylogenetic analysis. No specific clustering was demonstrated in RVAs detected from encephalitis/encephalopathy patients. Although the DS-1-like G1P[8] strain was predominant in both groups, no specific molecular characteristics were detected in RVAs from patients with severe central nervous system complications.

Human herpesvirus-6B infection in pediatric allogenic hematopoietic stem cell transplant patients: Risk factors and encephalitis.

BACKGROUND: Human herpesvirus-6B (HHV-6B) infection after allogenic hematopoietic stem cell transplantation (allo-HSCT) is known to be associated with post-transplant limbic encephalitis in adults. Meanwhile, the association between HHV-6B infection and central nervous system complications remains unclear in pediatric allo-HSCT patients. METHODS: In this study, HHV-6B infection was monitored for more than 50 days after HSCT using virus isolation and real-time PCR. Clinical information such as patient background and encephalitis status was collected retrospectively from medical records. Risk factors for HHV-6B infection were determined by the Cox proportional hazards model, and the clinical features of HHV-6B encephalitis in pediatric allo-HSCT patients were elucidated. RESULTS: Human herpesvirus-6B infection was observed in 74 (33.8%) of 219 patients at 3-47 days (median 18, interquartile range 13-20). Risk factors identified in multivariable analysis were hematological malignancy (hazards ratio [HR], 5.0; 95% confidence interval [CI], 2.3/12.5; P < .0001), solid tumor (HR, 4.8; CI, 1.5/16.3; P = .0104), unrelated donor (HR, 2.1; CI, 1.0/4.6; P = .0378), and sex-mismatched donor (HR 1.8; CI, 1.1/3.0; P = .0257). HHV-6B encephalitis occurred in only one of the 219 patients (0.46%); this patient demonstrated the typical clinical course of posterior reversible encephalopathy syndrome. CONCLUSION: Hematological malignancy, solid tumor, unrelated donor, and sex-mismatched donor were significant risk factors for HHV-6B infection after pediatric allo-HSCT. In pediatric allo-HSCT patients, the incidence of HHV-6B encephalitis was low and the clinical features differed from those in adult patients.

Persistent systemic rotavirus vaccine infection in a child with X-linked severe combined immunodeficiency.

OBJECTIVE: The main aims of the present study were to elucidate the systemic group A rotavirus (RVA) infection and to clarify the genetic changes of persistent virus in the X-linked severe combined immunodeficiency (SCID) patient. METHODS: RotaTeq vaccine (RV5) genotype-specific real-time reverse transcription polymerase chain reaction was used to monitor viral RNA load in serially collected serum and stool samples. Next-generation sequence analysis was used to determine the genotype of the virus by sequencing 11 gene segments. Polyacrylamide gel electrophoresis (PAGE) analysis was used to identify rearrangement of viral genes. The gene rearrangement was examined in NSP5 gene by using Sanger sequence. RESULTS: A 7-month-old boy demonstrated chronic diarrhea following the third administration of RV5 and failure to thrive. He was diagnosed with X-linked SCID and successfully underwent cord blood transplantation. High copy numbers of RV5 genotype G1 RNA were detected in serially collected stool and serum samples and the kinetics of viral RNA loads were correlated with the degree of clinical disease. Next-generation sequence analysis revealed genetic reassortment at least between the strains WI79-9/G1P7[5] and WI79-4/G6P1A[8] in the VP7 gene and the VP4 gene among the vaccine-derived rotavirus strains. In addition, PAGE analysis suggested genetic rearrangements in several genes, and it was confirmed in the NSP5 gene by sequence analysis. CONCLUSIONS: The kinetics of RVA RNA load in serum and stool samples was consistent with the clinical course of the patient. Among five genotypes of RV5 vaccine, G1 genotype replicated well in this patient. Reassortment and rearrangements were demonstrated in persistently infected G1 genotype of RV5.

Rotavirus Vaccination Can Be Performed Without Viral Dissemination in the Neonatal Intensive Care Unit.

Background: This study was conducted to assess the transmissibility of rotavirus vaccine strains after rotavirus vaccination in a neonatal intensive care unit (NICU). Methods: Pentavalent (RV5) or monovalent (RV1) rotavirus vaccine was administered to infants admitted to the NICU. Nineteen vaccinated infants and 49 unvaccinated infants whose beds were located in close proximity to the vaccinated infants were enrolled in this study. Dissemination and fecal shedding of vaccine viruses within the NICU were examined using real-time reverse transcription-polymerase chain reaction. Results: Shedding of the vaccine strain was detected in all 19 vaccinated infants. RV5 virus shedding started 1 day after the first vaccination and persisted for 8 days after the first vaccination, and viral shedding terminated by day 5 after administration of the second RV5 dose. The kinetics of RV1 virus shedding differed among vaccinated infants. The duration of RV1 virus shedding was longer after the first vaccination than after the second vaccination. In contrast to the vaccinated infants, no vaccine virus genomes were detected in any of the stool samples collected from the 49 unvaccinated infants. Conclusions: This study is direct evidence of no transmission of rotavirus vaccine strains between vaccinated infants and unvaccinated infants in close proximity within a NICU.

Chromosomally integrated human herpesvirus 6 in the Japanese population.

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.

Late-phase human herpesvirus 6B reactivation in hematopoietic stem cell transplant recipients.

BACKGROUND: We sought to determine whether late-phase human herpesvirus 6B (HHV-6B) infection in hematopoietic stem cell transplant (HSCT) recipients was associated with serious outcomes and mortality. METHODS: The occurrence and course of HHV-6B infection was monitored for at least 60 days after transplant using virus isolation and real-time polymerase chain reaction. Risk factors for late-phase HHV-6B infection were examined, and the propensity score was calculated with significant risk factors. The inverse probability-weighted multivariable logistic regression analysis was performed to estimate odds ratios (ORs) and the 95% confidence intervals (95% CI) for mortality. RESULTS: Late-phase HHV-6B infection was observed in 12/89 (13.5%) of the HSCT recipients. Older age (OR: 10.3, 95% CI: 2.1/72.9, P = .0027), hematologic malignancy (OR: 10.3, 95% CI: 1.8/97.1, P = .0063), unrelated donor transplantation (OR: 5.3, 95% CI: 1.1/36.0, P = .0345), and sex-mismatched donor transplantation (OR: 6.3, 95% CI: 1.4/39.5, P = .0149) were identified as risk factors for late-phase HHV-6B infection. Fifteen subjects died (17%). Inverse probability-weighted multivariable logistic model analysis revealed that late-phase HHV-6B infection was an independent risk factor for mortality (OR: 4.2, 95% CI: 1.7/11.0, P = .0012). Among 5 of the fatal cases of late-phase HHV-6B infection, viral infection might be associated with severe clinical manifestations. CONCLUSION: Late-phase HHV-6B infection in HSCT recipients was associated with worse outcomes. The full spectrum of clinical features of the infection has not been fully elucidated, and therefore, recipients with high-risk factors for late-phase HHV-6B infection should be carefully monitored.

Impact of Green Tea Catechin ECG and Its Synthesized Fluorinated Analogue on Prostate Cancer Cells and Stimulated Immunocompetent Cells.

Among the known or suspected risk factors, inflammation plays an important role in infectious and non-infectious pathways leading to cancer. Green tea polyphenols have been associated with reducing inflammation and protection against carcinogenesis, especially in prostate cancer. While most of the research in this field, so far, has focussed on epigallocatechin-3-O-gallate only, we studied epicatechin-3-O-gallate, the second most abundant green tea polyphenol with essential therapeutic potential, to obtain a more detailed understanding of its anti-tumor and anti-inflammatory action. Furthermore, to improve the bioactivity of (-)-epicatechin-3-O-gallate, we synthesized a difluoro analogue, called (-)-5,7-difluoro-epicatechin-3-O-gallate. Both compounds reduced cell proliferation of human primary inflammatory lymphocytes in an apoptosis-specific fashion, while (-)-5,7-difluoro-epicatechin-3-O-gallate had a significantly higher activity compared to the natural product (-)-epicatechin-3-O-gallate. Treatment of low-metastatic LNCaP and high-metastatic PC-3 prostate cancer cells with (-)-epicatechin-3-O-gallate and (-)-5,7-difluoro-epicatechin-3-O-gallate demonstrated a dose-dependent inhibition of cell viability in the low micromolar range. These effects suggest that (-)-epicatechin-3-O-gallate and the more effective (-)-5,7-difluoro-epicatechin-3-O-gallate could be therapeutically used to inhibit tumorigenesis during initiation, promotion, and progression by diminishing the amount of inflammation due to a reduction of inflammatory lymphocytes. Further studies are needed to prove this in in vivo experiments.

Case report of severe myocarditis in an immunocompromised child with Respiratory Syncytial Virus infection.

BACKGROUND: Respiratory syncytial virus (RSV) infection is common and may be severe among patients with preexisting cardiac anomalies, but direct involvement of myocardial damage is not common in those patients. Additionally, myocardial involvement has been rarely described among immune compromised children. CASE PRESENTATION: A 4-year-old girl with acute lymphoblastic leukemia who received maintenance chemotherapy in an outpatient clinic developed systemic inflammatory response syndrome. RSV infection was confirmed by a positive rapid antigen test and serological assay. Subsequently, she was diagnosed with severe myocarditis caused by RSV infection, which was diagnosed by abnormal findings of cardiac echography and ECG and elevated biomarkers for myocardial damage. Then, she was treated in the intensive care unit for 13 days. High amounts of RSV type B RNA was detected in tracheal aspirates and serum sample. CONCLUSION: This case report emphasizes that RSV infection may be associated with myocarditis in immunocompromised children receiving maintenance chemotherapy.

Survey of rotavirus-associated severe complications in Aichi Prefecture.

BACKGROUND: Rotavirus can, rarely, cause severe complications such as encephalopathy/encephalitis, myocarditis, sudden death, urinary stone, and gastrointestinal (GI) bleeding; and the incidence of these severe complications remains unclear. Additionally, it has not been determined whether rotavirus (RV) vaccine could reduce cases of severe complications or not. METHODS: A two-part questionnaire was designed to determine the number and clinical features of severe complications between 1 September 2008 and 31 August 2015, including the observation periods before and after RV vaccine introduction in Aichi Prefecture. RESULTS: Twenty-four cases of encephalitis/encephalopathy, eight cases of sudden death, three cases of urinary tract stone, and three cases of GI bleeding were reported during the 2008/2009 season and the 2012/2013 seasons. Although five cases of encephalitis/encephalopathy were reported, no other cases of severe complications were reported during the 2013/2014 and 2014/2015 seasons. No age difference was noted according to type of complication. Although onset of encephalitis/encephalopathy and of sudden death was around day 2 of illness, that of urinary tract stone and GI bleeding was slightly later (day 6 and day 4). In addition to the eight sudden deaths, fatal outcome was also noted in four cases (13.8%) of encephalitis/encephalopathy, and in one case of GI bleeding. CONCLUSION: According to the questionnaire survey in Aichi Prefecture, the incidence of the four severe RV-associated complications appears to have declined as the vaccination rate has increased.

Development of real-time RT-PCR assays for detection of three classes of HHV-6A gene transcripts.

Human herpesvirus 6 (HHV-6), a member of the betaherpesvirus family, has two distinct species: HHV-6A and HHV-6B. HHV-6B real-time reverse transcription polymerase chain reaction (RT-PCR) has been used to distinguish between active and latent viral infection. In this study, we developed a real-time RT-PCR assay to detect HHV-6A-specific transcripts and evaluated its reliability for analysis of clinical samples. To develop HHV-6A-specific real-time RT-PCR assays, three different classes of gene transcripts (immediate early: U90; early: U12; and late: U100) were selected as targets. Serial d ilutions of plasmid DNAs containing target sequences and RNAs extracted from HHV-6A-infected cells were used to determine assay specificity and sensitivity. Peripheral blood mononuclear cells (PBMCs) collected from patients with either primary or reactivated HHV-6B infection, and one patient with X-linked severe combined immunodeficiency (X-SCID) with HHV-6A reactivation, were used to evaluate assay reliability. The HHV-6A-specific real-time RT-PCR assays amplified plasmids containing the target sequences at concentrations between 10 and 1 × 106 copies per reaction. The intra-assay coefficients of variation were less than 5%. The three classes of HHV-6A gene transcripts were not detected in any HHV-6B sample isolated from the patients. In the X-SCID patient, high copy numbers of HHV-6A U12 and U100 transcripts were detected in PBMC samples during viremia. Thus, we successfully established highly sensitive and reproducible real-time RT-PCR methods targeting three classes of HHV-6A gene transcripts. This method should be useful for discriminating active HHV-6A infection from either latent infection or chromosomally integrated HHV-6A (ciHHV-6A).

Rotavirus genotypes and clinical outcome of natural infection based on vaccination status in the post-vaccine era.

Rotavirus (RV) is a leading cause of gastroenteritis in children. In Japan, Rotarix (RV1; GlaxoSmithKline), which is a monovalent vaccine derived from human RV (G1P[8]), has been introduced since November 2011, and RotaTeq (RV5; MSD) which is an pentavalent, human-bovine mono-reassortant vaccine (G1, G2, G3, G4, and P1A[8]), has been introduced since July 2012. Long-term follow-up on vaccine efficacy and RV genotypical change should be carried out in order to control RV infection. The RV gastroenteritis (RVGE) outbreak occurred during the 2018/2019 season in Aichi prefecture, Japan. Therefore, the molecular epidemiology of RV among three different groups of RVGE, which were outpatients who received RV1, those who received RV5, and those without vaccination, was explored. Clinical features of RVGE patients were compared among the three patient groups. Children less than 15 years of age with gastroenteritis who visited any of seven pediatric practices between January and June 2019 were enrolled in the study. G, P, and E genotypes were determined by direct sequencing of reverse transcription-polymerase chain reaction products amplified from stool samples. Among 110 patients, there were 27, 28, and 55 in the RV1-vaccinated, RV5-vaccinated, and unvaccinated groups, respectively. The most frequent genotype was G8P[8] (92/110 patients, 83.6%). Genotype distributions did not significantly differ among the three patient groups (P = .125). Mean Vesikari score was significantly lower among RV1-vaccinated (7.1) and RV5-vaccinated patients (6.4) than among unvaccinated patients (10.2) (P < .001). Even in RVGE patients treated in an outpatient clinic, RV vaccine reduced the severity of the disease in this cohort.

Evaluation of varicella vaccine effectiveness during outbreaks in schools or nurseries by cross-sectional study.

OBJECTIVE: The aim of this study was to elucidate vaccine effectiveness (VE) during varicella outbreaks in schools and nurseries in Japan. METHODS: An outbreak was defined as emergence of three or more cases of varicella within 21 days at the same institute. Clinical information such as varicella vaccination status, and history of varicella was collected. If a child had varicella during the outbreak, information about absences, fever, and disease severity was collected. RESULTS: From September 2018 to January 2020, four outbreaks were reported around our institute from three elementary schools and one nursery. A total of 676 children were analyzed in this study. Seventy-six children (11.2%) were unvaccinated, 309 (45.7%) had received one dose of vaccine, and 291 (43.0%) had received two doses. Most children in Pre-K2 (1-2 years old) to Pre-K6 (5-6 years old), who were the targets of the national immunization schedule, received two doses. Meanwhile, most children older than third grade received single dose. Seventy-five children (11.1%) had varicella. Varicella prevalence from Pre-K5 to the third grade was greater than 10%. The adjusted VEs of single- and two-dose of varicella vaccine were 57.8% and 89.0%. The number of days absent was significantly longer in unvaccinated children than single-dose recipients (P = 0.0145). Unvaccinated children had significantly more severe skin eruptions than single-dose recipients (P = 0.0046) and two-dose recipients (P = 0.0258). CONCLUSIONS: Although VEs of single-dose varicella vaccination during outbreaks was not high, the VE of two-dose vaccination was similar to that in a previously reported case-control study.

Effect of Lactococcus lactis Strain Plasma on HHV-6 and HHV-7 Shedding in Saliva: A Prospective Observational Study.

HHV-6 and HHV-7 can reactivate in the salivary gland in response to various host stresses. Lactococcus lactis strain Plasma (LC-Plasma) can activate plasmacytoid dendritic cells (pDCs) and decrease viral infection. We investigated whether LC-Plasma intake could decrease HHV-6 and HHV-7 reactivation in the salivary gland. A total of 54 healthy volunteers were enrolled in this study. Participants took LC-Plasma granules daily for 6 weeks. Saliva samples were collected from subjects weekly for 4 weeks before (first), during (second), and after (third period) LC-Plasma intake. There was a 2-week interval between the first and second periods and a 3-week interval between the second and third periods. Mean salivary HHV-6 and HHV-7 DNA loads were compared among the three observation periods. In the first period (baseline data of viral DNA shedding), HHV-6 DNA shedding was significantly higher in subjects under 40 years old, and HHV-7 DNA shedding was significantly higher in males. HHV-6 and HHV-7 DNA loads did not significantly differ between periods. Meanwhile, in a subgroup analysis of the subjects under 40 years old, HHV-6 DNA load was significantly lower in the second period than in the first period. LC-Plasma decreases HHV-6 reactivation in the salivary glands in younger adults.

Coinfection With Human Herpesvirus (HHV)-6B in Immunocompetent, Healthy Individuals With Chromosomally Integrated HHV-6A.

Immunocompetent sisters with chromosomally integrated human herpesvirus 6A (HHV-6A) transiently excreted HHV-6B genome in their saliva. They did not have past histories of exanthema subitum but had antibodies against HHV-6A and HHV-6B. This suggests that endogenous HHV-6A may modify the clinical features of HHV-6B coinfection.

Clinical Features of Complex Febrile Seizure Caused by Primary Human Herpesvirus 6B Infection.

BACKGROUND: It is well known that febrile seizures are commonly occur in children with exanthem subitum. In this study, we compared the clinical features and backgrounds of patients with complex febrile seizures with and without primary human herpesvirus 6B infection. METHODS: Sixty-two patients were enrolled after experiencing their first febrile seizure. Primary human herpesvirus 6B infection was confirmed when human herpesvirus 6B DNA was detected and human herpesvirus 6B antibody was negative in serum obtained during the acute phase of infection. Patient age, gender, and features of seizures were evaluated between patients with and without human herpesvirus 6B infection. RESULTS: Thirty patients with complex febrile seizure were diagnosed with primary human herpesvirus 6B infection. Those with primary human herpesvirus 6B infection (median, 13 months; range, seven to 39 months) were significantly younger than those without primary human herpesvirus 6B infection (median, 19 months; range, 10 to 59 months) (P = 0.001), and the proportion of males was significantly higher in patients without primary human herpesvirus 6B infection (male/female, 25/7) than in those with the infection (male/female, 14/16) (P = 0.017). An interval between fever onset and seizures of more than 24 hours was significantly more common in patients with primary human herpesvirus 6B infection (15 of the 30 patients) than in those without primary HHV-6B infection (two of 32 patients) (P < 0.001). CONCLUSIONS: A younger age at onset, a different gender ratio compared with febrile seizure due to other causes, and the length of interval between fever and seizures were features of complex febrile seizure associated human herpesvirus 6B infection. These findings may suggest a mechanism of complex febrile seizure onset different from that due to other causes.