吉川 哲史

INTRODUCTION: Insurance coverage for oral valganciclovir (VGCV) began in Japan in April 2023 on the basis of results, including our clinical trials for symptomatic congenital cytomegalovirus (CMV) disease. The VGCV treatment is available throughout Japan, so clinicians must consider the likelihood of hearing improvement and the possibility of neutropenia before dosing. MATERIALS AND METHODS: We performed a substudy of an investigator-initiated, single-arm, prospective, multicenter, clinical trial in which 24 infants with symptomatic congenital CMV disease were orally administered 16 mg/kg VGCV twice daily for 6 months as an intervention. We examined the infants' baseline characteristics associated with improved hearing impairment or a severely reduced neutrophil count. RESULTS: Of the 24 patients, 4 had normal hearing on assessment of their ear with the best hearing. Hearing impairment improved in 14 patients and did not respond to VGCV treatment in 6 patients at the 6-month hearing assessment. CMV DNA levels in plasma at baseline were higher in patients in whom hearing did not respond to treatment. A neutrophil count <500/mm3 occurred in 5 (21%) patients for the first 6 weeks and in 8 (33%) patients for the first 6 months. A neutrophil count at screening and the lowest neutrophil count over the 6 months showed the highest correlation (r = 0.477, p = 0.019). CONCLUSIONS: Infants with a low plasma viral load at screening tend to have an improvement in hearing impairment. Clinicians should be aware of neutropenia during VGCV treatment particularly in patients with a low neutrophil count during screening.

We encountered a previously healthy 3-year-old girl with interstitial pneumonitis that initially developed due to human adenovirus type 2 infection and exacerbated by primary human herpesvirus 7 infection. A comprehensive serum biomarker analysis showed patterns that differed by viral infection, suggesting that respiratory and lymphotropic viral infections might have different pathophysiology in interstitial pneumonitis.

Vaccine development for herpes simplex virus 2 (HSV-2) has been attempted, but no vaccines are yet available. A plasmid-based reverse genetics system for Rotavirus (RV), which can cause gastroenteritis, allows the generation of recombinant RV containing foreign genes. In this study, we sought to develop simian RV (SA11) as a vector to express HSV-2 glycoprotein D (gD2) and evaluated its immunogenicity in mice. We generated the recombinant SA11-gD2 virus (rSA11-gD2) and confirmed its ability to express gD2 in vitro. The virus was orally inoculated into suckling BALB/c mice and into 8-week-old mice. Serum IgG and IgA titers against RV and gD2 were measured by ELISA. In the 8-week-old mice inoculated with rSA11-gD2, significant increases in not only antibodies against RV but also IgG against gD2 were demonstrated. In the suckling mice, antibodies against RV were induced, but gD2 antibody was not detected. Diarrhea observed after the first inoculation of rSA11-gD2 in suckling mice was similar to that induced by the parent virus. A gD2 expressing simian RV recombinant, which was orally inoculated, induced IgG against gD2. This strategy holds possibility for genital herpes vaccine development.

UNLABELLED: This study aimed to identify the appropriate dose of aspirin to be prescribed to patients with acute Kawasaki disease (KD). Using a Japanese national inpatient database, we identified patients with KD treated with intravenous immunoglobulin between 2010 and 2021.The outcomes included the occurrence of coronary artery abnormalities and intravenous immunoglobulin resistance, length of hospital stay, and medical costs. Restricted cubic spline functions were performed to examine the association between aspirin dose and the outcomes. Data of 82,109 patients were extracted from the database. Non-linear associations were observed between aspirin dose and the outcomes. In comparison with an aspirin dose of 30 mg/kg/day, the odds ratio (95% confidence interval) for coronary artery abnormalities was 1.40 (1.13-1.75) at 5 mg/kg/day. An aspirin dose of ≥ 30 mg/kg/day did not significantly change the odds ratio for coronary artery abnormalities. Intravenous immunoglobulin resistance was significantly lower at a dose of 60 mg/kg/day or higher. CONCLUSION:  The results showed no significant association between aspirin escalation over standard-dose and coronary artery abnormalities in patients with acute KD. High-dose aspirin showed the potential to reduce hospital stay and medical costs without increasing complications. WHAT IS KNOWN: • Aspirin is used as a standard treatment together with intravenous immunoglobulin for acute Kawasaki disease (KD). However, few studies have shown the most effective dosage of aspirin to prevent coronary artery abnormalities (CAAs). WHAT IS NEW: • There was no significant association between aspirin dose escalation and CAAs in patients with acute KD.

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.

OBJECTIVES: Intestinal rotavirus (RV) vaccine replication and host immune response are suggested to be affected by several factors, including maternal antibodies, breastfeeding history, and gut microbiome, which are thought to be similar in pairs of twins. The aim of this study was to determine whether viral shedding from the fecal RV vaccine strain Rotarix® (RV1) and IgG and IgA responses to RV show similarity in pairs of twins. METHODS: Quantitative reverse transcription polymerase chain reaction specific to RV vaccine strain RV1 was used to monitor fecal RV1 viral shedding. RV IgG and IgA titers were measured using an in-house enzyme-linked immunosorbent assay. Fecal RV1 viral shedding and immune responses were compared between twins and singletons with mixed effects and fixed effects models. RESULTS: A total of 347 stool and 54 blood samples were collected from four pairs of twins and twelve singletons during the observation period. Although the kinetics of fecal RV1 viral shedding and immune responses differed among vaccinated individuals, they appeared to be similar within twin pairs. RV shedding after the first dose (P=0.049) and RV IgG titers during the entire observation period (P=0.015) had a significantly better fit in the fixed effect model that assumed that twins have the same response versus the model that assumed that twins have a different response. CONCLUSIONS: The similarity of RV vaccine viral replication in intestine and host immune responses in twin pairs was demonstrated using statistical analysis.

Abstract Nonpharmaceutical interventions (NPIs) to control COVID‐19 have decreased the incidence of many pediatric infectious diseases. The epidemiology of β‐ and γ‐herpesvirus infections might have been affected by NPIs. The aim of this study was to elucidate changes in trends in β‐ 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.

Several studies have shown an association between varicella-zoster virus infection and ischemic stroke. We analyzed the trends in the numbers of patients with varicella, herpes zoster and ischemic stroke before and after the universal vaccination program using a Japanese database of hospitalized patients. The number of patients with varicella decreased but those of herpes zoster and ischemic stroke did not change.

We report an autopsy case of anti-N-methyl-D-aspartate (NMDA) receptor (NMDAR) encephalitis with concurrent human herpes virus-6 (HHV-6) A deoxyribonucleic acid (DNA) detection in cerebrospinal fluid (CSF). A 38-year-old previously healthy Japanese man presented with a generalized seizure. Brain magnetic resonance imaging (MRI) findings were unremarkable, but CSF revealed pleocytosis. On Day 11, HHV-6 DNA was detected in CSF, and IgG antibodies against the NR1 subunit of the NMDAR (GluN1) were subsequently detected. Since HHV-6 encephalitis was initially suspected, the patient was treated with foscarnet and ganciclovir, but the HHV-6A copy number increased from 200 (Day 22) to 2000 copies/mL (Day 47), and the therapy was ineffective. As typical symptoms of anti-NMDAR encephalitis developed, we changed the patient's treatment to combat anti-NMDAR encephalitis. He was repeatedly treated with first-line immunotherapy, and GluN1 antibody titer decreased. He was not treated with second-line immunotherapy because of recurrent infections; he died on Day 310. Postmortem examinations did not show systemic tumors. Microscopic examination of the brain revealed only severe neuronal rarefaction in the hippocampal cornu ammonis (CA) 3-4 areas with gliosis. Early initiation of aggressive immunotherapy may be required in a refractory case of anti-NMDAR encephalitis, even with HHV-6A DNA detection, because the significance of this concurrent detection in autoimmune encephalitis remains unclear.

Central nervous system (CNS) involvement in anaplastic large cell lymphoma (ALCL) at diagnosis is rare and leads to poor prognosis with the use of the standard ALCL99 protocol alone. CNS-directed intensive chemotherapy, such as an increased dose of intravenous MTX, increased dose of dexamethasone, intensified intrathecal therapy, and high-dose cytarabine, followed by cranial irradiation, has been shown to improve survival in this population. In this paper, the authors describe a 14-year-old male with an intracranial ALCL mass at onset who received CNS-directed chemotherapy followed by 23.4 Gy of whole-brain irradiation. After the first systemic relapse, the CNS-penetrating ALK inhibitor, alectinib, was applied; it has successfully maintained remission for 18 months without any adverse events. CNS-penetrating ALK inhibitor therapy might prevent CNS relapse in pediatric ALK-positive ALCL. Next-generation ALK inhibitors could be introduced as a promising treatment option, even for primary ALCL with CNS involvement, which could lead to the omission of cranial irradiation and avoid radiation-induced sequalae. Further evidence of CNS-penetrating ALK inhibitor combined therapy for primary ALK-positive ALCL is warranted to reduce radiation-induced sequalae in future treatments.

予防接種後有害事象(AEFI)および予防接種ストレス関連反応(ISRR)に関連する動画講義視聴が小児科医の予防接種に対する知識、態度、自信、役割認識、自己効力感、行動に与える影響を調査した。介入前評価(pre study)に回答した日本小児科学会会員368名をA群とB群に分けてA群にのみオンラインでISRRに関する約20分間の動画講義を配布し、pre studyから約1ヵ月後にA群・B群に介入後評価(Post study)を行った。Post studyの回答者A群74名、B群95名を対象に動画講義視聴による介入効果について検討した。その結果、AEFIおよびISRRに関連する調査によってA群・B群の知識レベルが向上したが、予防接種に対する態度、自信、役割認識、自己効力感、実際の接種行動に与える影響は限定的であった。

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.

BACKGROUND: Congenital cytomegalovirus (CMV) infection (cCMV) can cause sensorineural hearing loss and neurodevelopmental disabilities in children. Oral valganciclovir (VGCV) therapy has been reported to improve long-term audiological and neurodevelopmental outcomes in patients with cCMV. The levels of CMV DNA in whole blood have been monitored in previous studies. However, quantitative methods using whole blood have not been standardized. Recently, the plasma viral load has been standardized and widely used in CMV-associated diseases. METHODS: CMV viral loads in whole blood and plasma were serially measured in 24 patients with a confirmatory diagnosis of cCMV during oral VGCV therapy using an in-house real-time PCR assay. Plasma samples were assayed using the Cobas 6800 system (Roche Diagnostics) in addition to an in-house assay. RESULTS: Plasma CMV viral loads were remarkably decreased at the end of therapy compared to before therapy. A significant correlation of CMV levels between whole blood and plasma was observed (Spearman's ρ = 0.566). The levels of CMV DNA before therapy were significantly correlated with the period of decreasing the viral loads to below the detection limit, not only in whole blood (Spearman's ρ = 0.901) but also in plasma (Spearman, ρ = 0.804). Finally, CMV viral loads between the in-house assay and commercially available standardized assay in 75 plasma samples with positive PCR results for CMV were compared; a significant correlation was observed between the results of both assays. CONCLUSIONS: There was a significant correlation between the two assays (Spearman, ρ = 0.882), suggesting that CMV plasma viral loads measured by the standardized assay are widely used to monitor the levels of CMV DNA in patients with cCMV during oral VGCV therapy.

Eczema herpeticum (EH) is a disseminated cutaneous infection with herpes simplex virus (HSV) that develops in patients with atopic dermatitis. The kinetics and clinical significance of HSV viremia in EH are poorly understood. Herein, we report HSV DNAemia in a child with EH 12 months after the completion of chemotherapy for Hodgkin lymphoma.

Multisystem inflammatory syndrome in children (MIS-C) has been widely reported, mainly in Western countries. The clinical features of MIS-C and Kawasaki disease are similar. The latter is common in Asian countries, including Japan. Meanwhile, the incidence of MIS-C seems to be low in Japan. Retropharyngeal edema is relatively common in older patients with Kawasaki disease and has been reported in a few patients with MIS-C. We describe a case of severe retropharyngeal edema after coronavirus disease 2019 (COVID-19) that improved quickly with high-dose of intravenous immunoglobulin treatment. Onset of retropharyngeal edema was 3 weeks after COVID-19. The patient received appropriate intravenous antibiotics for 5 days, but his symptoms worsened. Therefore, we suspected that his retropharyngeal edema was caused by suspected MIS-C even though he did not have the typical clinical symptoms of suspected MIS-C such as gastrointestinal symptoms and shock. Retropharyngeal edema was refractory to antibiotic therapy but lessened quickly with high-dose immunoglobulin therapy, without other typical clinical manifestations of MIS-C, suggesting that early immunoglobulin therapy might prevent the progression of MIS-C.

BACKGROUND: Scholarship is recognized as important in residency training worldwide. The Japan Pediatric Society (JPS) enacted a reform in 2017 to require publication of an article as a prerequisite for taking the board certification test, with the goal of increasing scholarly activity. METHODS: The purpose of this study was to provide a detailed description of the trends in residents' scholarly activities related to the JPS reform. A secondary analysis was performed on the cross-sectional database of pediatrics residents who took the certification test in 2015-2018. RESULTS: The enrolled participants were 2399 residents of which 79.7% passed the test. Publication of any type of article increased significantly (21%-22% to 100%; 0.1 to 0.3/person-year) after the implementation of the JPS reform, whereas academic presentations did not (89% to 91%; 1.2 to 1.3/person-year), both in terms of the percentage of the number of those who created them and the average rate of research production. Not only Japanese articles (11%-13% to 49%-53%; 0.04 to 0.15-0.17/person-year) or case reports (10%-14% to 51%-52%; 0.03-0.05 to 0.16-0.17/person-year), but also English articles (4%-5% to 15%-16%; 0.01-0.02 to 0.05/person-year) and original articles (5% to 11%-17%; 0.01 to 0.03-0.05/person-year) increased significantly. The number of each type of article publication was correlated with success in the board certification test (odds ratio 1.5-1.8). CONCLUSIONS: Scholarly activities of pediatrics residents were enhanced by the JPS implementation of the article requirement policy, which is crucial to fostering a scholarly culture. The most efficient measures to promote scholarship need to be persistently investigated.

BACKGROUND: Although many child death review (CDR) systems have been developed in Japan, the optimal system is still being identified. The aim of this study is to identify the etiologies of child deaths and to propose a screening method for initiating the CDR process in Japan. METHODS: Clinical medical records (CMRs) in hospitals and autopsy records were surveyed for cases of deaths of children aged less than 15 years between 2014 and 2016 in Aichi Prefecture, Japan. The data were analyzed in three steps, and the findings were compared with the vital statistics. RESULTS: Of the 695 children whose death certificates were submitted to Aichi Prefecture, 590 could be traced to pediatric care hospitals. The distribution of causes of death was slightly different from the vital statistics, with 11.5% dying of extrinsic causes and 19.7% dying of unknown causes. Maltreatment was suspected in 64 cases, which was much higher than that in government statistics. Overall, 158 (26.8%) deaths were considered preventable. The number of unnatural deaths, which might be screened in, was calculated as 172 (29.2%) in the vital statistics, whereas the survey of CMRs revealed that 241 (40.8%) to 282 (47.8%) should be screened in. CONCLUSIONS: Surveying CMRs in hospitals may be a suitable method to detect and screen deaths to start the CDR process in Japan.

2020年2月～2022年4月に専用データベースに報告された小児コロナウイルス感染症2019患者のうち、0～15歳の5411例(男児2889例、女児2522例)の急性期における臨床的特徴を解析した。オミクロン株流行により感染経路は家庭内感染から学校・幼稚園・保育所へ変化した。オミクロン株流行期に初発症状でけいれん発作を起こした割合は1～4歳で13.4%、5～11歳で7.4%、オミクロン株流行期に初発症状で悪心・嘔吐を認めた割合は1～4歳で12.2%、5～11歳で22.6%、12～15歳で14.6%であり、いずれもデルタ株流行前またはデルタ株流行期と比較して大幅に増加した。最終的に全体の約2%にけいれんを伴う合併症が報告された。肺炎の合併率は変異株の違いによる変化をほとんど認めなかった。発症後28日を超えた症例報告書が提出された1697例(男児899例、女児798例、年齢中央値6.3歳)のうち、55例(3.2%)に発症後28日を超えても何らかの症状が残存した。

国内の地域偏在を調整後に無作為に抽出した小児科1次医療施設100施設、2次医療施設100施設と全ての3次医療施設119施設を候補として、2020年4月(I期)、2020年10月(II期)、2021年4月(III期)の各時点における診療体制についてインターネットを介してアンケート調査した。回答があったのは1次医療施設27施設(回答率27%)、2次医療施設19施設(回答率19%)、3次医療施設72施設(回答率61%)であった。発熱患者の診療応需についてはコロナウイルス感染症2019(COVID-19)接触歴を有する場合、1次医療施設で応需困難となったのはI期で29.6%であったが、II期22.2%、III期14.8%と経時的に減少した。COVID-19患者の診療体制はIII期においても3次医療施設の約半数で軽症・無症状患者の診療が応需されていた。面会制限は大多数の施設で導入され、面会禁止とした施設がIII期においても2次医療施設の63.2%、3次医療施設の38.9%で存在した。

Mutations in transport and Golgi organization 2 homolog (TANGO2) have recently been described as a cause of an autosomal recessive syndrome characterized by episodes of metabolic crisis associated with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration. Herein, we report a case of a one-and-a-half-year-old Japanese girl, born to nonconsanguineous parents, who presented with metabolic crisis characterized by hypoglycemia with hypoketonemia, rhabdomyolysis, lactic acidosis, and prolonged corrected QT interval (QTc) at the age of 6 months. Acylcarnitine analysis during the episode of crisis showed prominent elevation of C14:1, suggesting very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. In addition, worsening rhabdomyolysis was observed after intravenous administration of L-carnitine. VLCAD deficiency was initially suspected; however, the enzyme activity in lymphocytes was only mildly decreased at the gene carrier level, and no mutation in the VLCAD gene (ADADVL) was detected. Subsequently, acylcarnitine analysis was nonspecific at 17-h fasting and almost normal during the stable phase. Eventually, a trio whole-exome sequencing revealed a compound heterozygous variant of two novel variants in the TANGO2 gene, a missense variant, and a deletion of exon 7. This is the first case of TANGO2 deficiency in Asians. Our case suggests that elevated C14:1 may be seen in severe metabolic crises and that the use of L-carnitine should be avoided during metabolic crises.

We performed virological analysis of resected brain tissues from a patient with temporal lobe epilepsy associated with mesial temporal sclerosis after febrile status epilepticus caused by human herpesvirus 6 infection. The patient had febrile status epilepticus at 9 months of age associated with human herpesvirus 6 infection. Magnetic resonance imaging revealed reduced water diffusion in the right temporal lobe and hippocampus. Polymerase chain reaction analysis detected 1.6 × 105 copies/μg of human herpesvirus 6 DNA in whole blood, but none in the cerebrospinal fluid. The patient developed temporal lobe epilepsy associated with mesial temporal sclerosis at 67 months of age, necessitating surgical treatment. Anterior temporal lobectomy was performed at 171 months of age. Real-time polymerase chain reaction analysis of resected brain tissues revealed no viral DNA. In our patient, human herpesvirus 6 infection triggered febrile status epilepticus, while direct evidence to prove contribution of HHV-6 to the development of MTS was not obtained.

Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited disorder of branched-chain amino acid metabolism caused by mutations in BCKDHA, BCKDHB, and DBT that encode the E1α, E1β, and E2 subunits of the branched-chain α-ketoacid dehydrogenase (BCKD) complex. Various MSUD-causing variants have been described; however, no structural rearrangements in BCKDHA have been reported to cause the classic MSUD phenotype. Here, we describe the classic patient with MSUD with compound heterozygous pathogenic variants in BCKDHA: a missense variant (NM_000709.3:c.757G > A, NP_000700.1:p.Ala253Thr) and a paracentric inversion disrupting Intron 1 of BCKDHA, which was identified by whole-genome sequencing and validated by fluorescence in situ hybridization. Using the sequence information of the breakpoint junction, we gained mechanistic insight into the development of this structural rearrangement. Furthermore, the establishment of junction-specific polymerase chain reaction could facilitate identification of the variant in case carrier or future prenatal/preimplantation tests are necessary.

We analyzed serially collected serum samples from healthy adults who underwent BNT162b2 vaccination to elucidate the association between spike (S)-IgG antibody titers determined by ELISA using the WHO international standard (NIBSC code 20/136) and neutralizing antibody titers against three live SARS-CoV-2 variants. This study included 53 health care workers who received two doses of the BNT162b2 vaccine. S-IgG and nucleocapsid (N)-IgG antibody titers were measured by ELISA. Neutralizing (NT) antibody responses against three variants (Wuhan D614 G: KUH003, Alpha, and Delta) were evaluated before and after the first and second vaccination. N-IgG were not detected in any serum samples. S-IgG antibody titers remarkably increased after two BNT162b2 vaccine doses in all participants. S-IgG antibody titers were strongly correlated with NT titers against three variants of live viruses: KUH003 (r = 0.86), Alpha (r = 0.72), and Delta (r = 0.84). Serum samples from participants after one dose of BNT162b2 neutralized Alpha efficiently (median titer, 113.0), but median NT titers against KUH003 and Delta variants were lower, 57.0 and 28.0, respectively (p < .01). Two doses of the BNT162b2 vaccine elicited a strong immune response in this study. The second dose was required for induction of a strong booster effect. Serum collected from BNT162b2 vaccine recipients contained significantly lower neutralizing activity against Delta than that of against KUH003 (p < .0001) and Alpha (p < .0001). If a new variant emerges, live virus-based NT titers should be examined in serum obtained from vaccine recipients to evaluate vaccine efficacy for protection against infection.

Our aims were to determine the clinical impact of oral valganciclovir (VGCV) in infants aged ≤2 months with congenital cytomegalovirus (CMV) disease and evaluate the efficacy of VGCV when initiated beyond the neonatal period. The multicenter, single-arm, open-label clinical trial was conducted in Japan. Twenty-five infants aged ≤2 months with congenital CMV disease involving the central nervous system were enrolled and treated with VGCV for 6 months. The primary endpoint was the change in the whole blood CMV load before and after treatment. The secondary endpoint was the change in the auditory brainstem response (ABR) before and after treatment. Changes in ABR were assessed between the younger and older age groups (≤ and &gt;30 days at treatment initiation). Of the 25 patients, one was excluded owing to epilepsy before VGCV administration. The median change in the CMV DNA level in whole blood was -246.0 IU/mL. The best ear and total ear assessments based on ABR were categorized as (improved + unchanged) after treatment for 100% and 93.8%, respectively. No differences in hearing efficacy were observed between the younger and older age groups. Oral VGCV is a potential therapeutic option for treating infants aged ≤2 months with congenital CMV disease.

Objectives: Fish roe is a common allergen in Japan. We have previously reported that although immunoglobulin (IgE) from patients with salmon roe (SR) or pollock roe (PR) allergies cross-react, 70% of patients with SR allergy can consume PR without developing any symptoms. However, a correlation between clinical cross-reactivity and serological cross-reactivity remains to be demonstrated. Methods: Serum samples were collected from 15 patients with SR allergy who had consumed cooked PR previously. Among these volunteers, four had experienced immediate symptoms after consuming cooked PR, while the others had exhibited no symptoms of PR allergy. A competitive enzyme-linked immunosorbent assay (ELISA) was performed to analyze the serological cross-reactivity with SR and PR. Immunoblotting inhibition assays were performed using serum samples that had been pre-incubated with SR or PR extracts. Results: In ELISAs, binding to SR was inhibited by >50% when the serum samples from patients with both SR and PR allergies were pre-incubated with PR extract (p=0.0256). In immunoblots, pre-incubation of serum samples with PR extract inhibited detection of the 16-kDa protein, which likely corresponds to the major SR allergen beta' component, significantly more for samples from patients with both SR and PR allergies (100%) than for samples from those with only an SR allergy (18.2%) (p=0.011). Conclusions: The superior competitive binding of the sera from patients with both SR and PR allergies to PR compared with that to SR may induce clinical cross-reactivity between SR and PR.

This case showed a 13-year-old boy presented with calvarium subperiosteal hematoma crossing the suture lines caused by hair pulling, and 3D-CTV can differentiate calvarium subperiosteal hematoma crossing the suture lines from subgaleal hematoma. He was treated successfully.

BACKGROUND: Kawasaki disease (KD) is an acute, febrile, systemic vasculitis of unknown etiology that primarily affects the coronary arteries and generally occurs at around 1 year of age. Although the diagnosis of KD is generally not difficult, it is challenging in cases of incomplete KD lacking characteristic clinical manifestations. The incidence of incomplete KD is higher in infants younger than 6 months of age. Pneumonia is an extremely rare complication of KD and can be misinterpreted as atypical pneumonia rather than KD. Herein, we report a neonate with atypical KD and severe pneumonia who required mechanical ventilation. CASE PRESENTATION: Japanese one-month-old infant had only fever and rash on admission (day 1), and he was transferred to the intensive care unit for severe pneumonia on day 2. Although pneumonia improved following intensive care, he was diagnosed with KD on day 14 because of emerging typical clinical manifestations such as fever, bulbar nonexudative conjunctival injection, desquamation of the fingers, and coronary artery aneurysm. KD symptoms improved after three doses of intravenous immunoglobulin plus cyclosporine. However, small coronary aneurysms were present at the time of discharge. In a retrospective analysis, no pathogens were detected by multiplex real-time PCR in samples collected at admission, and the serum cytokine profile demonstrated prominent elevation of IL-6 as well as elevation of neopterin, sTNF-RI, and sTNF-RII, which suggested KD. CONCLUSIONS: The patient's entire clinical course, including the severe pneumonia, was caused by KD. As in this case, neonatal KD may exhibit atypical manifestations such as severe pneumonia requiring mechanical ventilation.

OBJECTIVES: Reactivation of Betaherpesvirinae (Human herpesvirus 6A: HHV-6A, -6B, HHV-7) may be associated with mental illness and host fatigue. This study aimed to determine whether viral reactivation, measured by monitoring salivary viral DNA load, can be used to monitor depression in pregnant and postpartum women. METHODS: Saliva samples were collected from 64 pregnant women at five-point of observation periods. The HHV-6 and HHV-7 specific qPCRs were carried out to measure viral DNA load. When HHV-6 DNA was detected in saliva, nested PCR was used to discriminate between HHV-6A and B. RESULTS: In both viruses, a significant correlation was observed between detection frequency and viral DNA load in saliva. In the low-shedding group, HHV-6 DNA was significantly higher in the third trimester (P<0.0001), the time of delivery (P=0.0003), one month after birth (P=0.0023) compared to the first trimester, and HHV-7 was at the time of delivery (P=0.0277) and one month after birth (P=0.0235). Most of detected HHV-6 DNAs in saliva were HHV-6B. Both viral DNA loads were significantly lower (HHV-6:P=0.0101, HHV-7:P=0.0044) in the subjects with abnormal EPDS scores. CONCLUSIONS: Detection rate and viral DNA load of both viruses in saliva increased after the third trimester. Salivary virus DNA shedding was significantly lower in subjects with an abnormal EPDS score. This article is protected by copyright. All rights reserved.

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.

LAMP法は等温での遺伝子増幅を特徴とする分子生物学的診断法である。目視もしくは専用の測定機器でリアルタイムに標的遺伝子の増幅を判定できることから、臨床現場での遺伝子検査だけでなく食品、環境等さまざまな領域での遺伝子検査に応用されている。われわれは水痘帯状疱疹ウイルス感染症診断において、DNA抽出を必要としないdirect LAMP法を構築、さらにLAMP増幅産物をRFLP解析することによりワクチン株と野生株の型判別を可能にした。自然水痘と水痘ワクチン接種後罹患(breakthrough varicella)症例の診断におけるdirect LAMP法の感度は、それぞれ93.3%と84.4%であった。PCR法は病原微生物遺伝子診断のゴールドスタンダードと考えられるが、LAMP法は特別な機器を必要とせず、簡便かつ迅速に検査可能な点が利点としてあげられる。さらにdirect LAMP法は、ベッドサイドにおけるPOCTとしての有用性が非常に高い検査法である。(著者抄録)