吉川 哲史

症例は5歳男児で、ブリッジの体勢を10秒間保持した後、後方倒立回転飛び(バック転)を行った直後に腰痛が出現した。安静にして様子をみていたが徐々に症状は増悪し、約1時間後に起立できなくなった。約半日後に尿閉が出現したため緊急入院した。体温36.7℃、血圧110/57mmHg、脈拍85/分、SpO2は98%、胸腹部に異常所見を認めなかった。意識清明、小脳機能、脳神経系および上肢に異常所見を認めなかった。下肢の徒手筋力テスト(MMT)は両側とも1〜2程度で、筋力低下を認めた。両側膝蓋腱反射・アキレス腱反射はともに低下していた。両側Babinski反射は陽性であった。感覚障害は認めなかった。膀胱直腸障害を認め、肛門の感覚は残っていたが肛門括約筋収縮は減弱していた。血液、髄液検査ともに以上を認めず、髄液検査ではミエリン塩基性蛋白、オリゴクローナルIgGバンドは陰性であった。胸腰椎単純X線、胸腰椎単純CTでは骨折を認めず、胸腰椎MRIでT1強調像では異常信号を認めなかったがT2強調矢状断ではTh9から脊髄円錐にかけ髄内に長軸方向に伸びる高信号域を認めた。ステロイドパルス療法を行い第23病日に正常化した。

Background: Rotavirus can cause severe complications such as encephalopathy/encephalitis and sudden unexpected death. The incidence of rotavirus-associated encephalopathy/encephalitis or sudden unexpected death remains unknown. To clarify the clinical features of rotavirus-associated encephalitis/encephalopathy and sudden unexpected death, we conducted a nationwide survey in Japan. Method: A two-part questionnaire was designed to determine the number of the cases and the clinical features of severe cases of rotavirus infection, including encephalitis/encephalopathy and sudden unexpected death, between 2009 and 2011. Result: Of the 1365 questionnaires sent to hospitals, 963 (70.5%) were returned and eligible for analysis. We determined 58 cases of rotavirus-associated encephalitis/encephalopathy and 7 cases of sudden unexpected death. These patients were diagnosed with rotavirus infection by immunochromatography. Although 36/58 (62.1%) encephalitis/encephalopathy patients had no sequelae, 15/58 (25.9%) patients had neurological sequelae, and 7/58 (12.1%) patients had fatal outcomes. Pleocytosis was observed in 9/40 (22.5%) patients and cerebrospinal fluid protein levels were elevated in only 4/40 (10%) patients. Elevated lactate dehydrogenase (LDH) (>500 IU/L) or acidemia (pH <7.15) were related to a poor prognosis. Conclusion: We estimate that annual cases of rotavirus-associated encephalitis/encephalopathy and sudden unexpected death were 44.0 and 4.9 cases in Japan, respectively. Elevated LDH (>500 IU/L) or acidemia (pH < 7.15) were related to a poor prognosis of the encephalitis/encephalopathy. (C) 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The reliability of the HHV-6B LAMP using the dry-reagent method was evaluated using serum samples obtained from febrile children. The sensitivity of the original and dry-reagent methods was 10 copies/reaction and 100 copies/reaction, respectively. The dry-reagent LAMP method was highly sensitive (94.0%) and specific (96.0%) for the detection of HHV-6B. (C) 2014 Elsevier B.V. All rights reserved.

Approximately 1 percent of healthy individuals carry human herpesvirus-6 within a host chromosome. This is referred to as chromosomally integrated herpesvirus-6 (CIHHV-6). In this study, we investigated the chromosomal integration site in six individuals harboring CIHHV-6B. Using FISH, we found that HHV-6B signals are consistently located at the telomeric region. The proximal endpoints of the integrated virus were mapped at one of two telomere-repeat-like sequences (TRSs) within the DR-R in all cases. In two cases, we isolated junction fragments between the viral TRS and human telomere repeats. The distal endpoints were mapped at the distal TRS in all cases. The size of the distal TRS was found to be similar to 5 kb which is sufficient to fulfill cellular telomeric functions. We conclude that the viral TRS in the DR regions fulfill dual functions for CIHHV-6: homology-mediated integration into the telomeric region of the chromosome and neo-telomere formation that is then stably transmitted.

Acute encephalopathy with biphasic seizures and late reduced diffusion has become increasingly common among various types of human herpesvirus 6B (HHV-6B) encephalitis at the time of primary viral infection. The aim of the present study is to explore the pathophysiology of HHV-6B-associated acute encephalopathy with biphasic seizures and late reduced diffusion. Five cytokines and five chemokines were measured in serum and cerebrospinal fluid (CSF) obtained from 12 HHV-6B-associated acute encephalopathy with biphasic seizures and late reduced diffusion patients and 19 control exanthem subitum (without complications) patients. Serum interleukin (IL)-10 (P=0.007) and IL-8 (P=0.025) were significantly higher in the patients with the disease than controls. Serum IL-1 (P=0.034) and monocyte chemoattractant protein (MCP)-1 (P=0.002) were significantly higher in the controls than patients with the disease. In patients with the disease, IL-10 (P=0.012), regulated on activation normal T cell expressed and secreted (RANTES; P=0.001), and monokine induced by interferon (MIG; P=0.001) were significantly higher in serum than CSF, meanwhile IL-6 (P=0.034), IL-8 (P=0.034), and MCP-1 (P=0.001) were significantly higher in CSF than serum. Additionally, serum IL-10 was significantly higher in the disease patients with sequelae than those without sequelae (P=0.016). Several cytokines and chemokines may be associated with the pathogenesis of acute encephalopathy with biphasic seizures and late reduced diffusion. Moreover, the regulation of cytokine networks appears to be different between peripheral blood (systemic) and central nervous system. J. Med. Virol. 86:512-518, 2014. (c) 2013 Wiley Periodicals, Inc.

Cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and 7 (HHV-7) are important pathogens in immunocompromised patients. To elucidate the kinetics of the three -herpesviruses in saliva and urine samples were collected serially from children with renal diseases. Twenty children with renal diseases were enrolled in this study. A total of 240 saliva and urine samples were collected monthly from the patients over a 1-year period. Viral DNAs loads were measured by real-time PCR. In 10 CMV seropositive patients CMV DNA was detected rarely in saliva and CMV DNA load was lower than the other two -herpesviruses DNA loads. All patients were seropositive for HHV-6B and the virus was detected frequently in saliva. Two of 20 patients were HHV-7 seronegative. High copies of viral DNA were detected continuously in saliva of the HHV-7 seropositive patients. Although neither CMV nor HHV-6B DNA load was different among the three renal diseases, HHV-7 DNA load was different among the diseases (P=0.039). HHV-6B DNA loads were significantly higher in patients with immunosuppressive treatment compared to those without treatment (P=0.013). Although CMV DNA was detected in urine samples collected from 5 of 10 CMV seropositive patients, HHV-6B and HHV-7 DNA were detected at relatively low frequencies in urine. No remarkable temporal associations between viral DNA excretion and proteinuria or immunosuppressive treatment were demonstrated. The pattern of viral DNA excretion in saliva and urine were different among the three viruses. No temporal correlation was observed between viral infection and renal diseases. J. Med. Virol. 86:505-511, 2014. (c) 2013 Wiley Periodicals, Inc.

改良型抗麻疹IgM検出試薬(B法)の信頼性を評価するため、突発性発疹患児から採取したペア血清を用いて現行試薬(A法)と比較した。A法では80検体中26検体(32.5%)で陽性・判定保留となったのに対し、改良法であるB法では80検体中10検体(12.5%)が陽性・判定保留となった。改良法であるB法でも陽性・判定保留となった患児7例中5例が発症1ヵ月前以内にMRワクチン接種を受けていた。(著者抄録)

In order to determine whether mixed infections of human herpesvirus 6B (HHV-6B) occur in immunocompetent and immunocompromised individuals, we examined the copy numbers of telomeric repeat sequences (TRS) of clinical isolates. In clinical isolates obtained from patients with exanthem subitum caused by primary HHV-6B infection, PCR products with HHV-6B TRS ranging between 400 and 800 bp were amplified. PCR products of various sizes were amplified in four clinical isolates from drug-induced hypersensitivity syndrome (DIHS) patients and 15 isolates from hematopoietic stem cell transplant (HSCT) recipients with HHV-6B reactivation. Based on the sequence analysis of the PCR products, the copy numbers of TRS in DIHS and HSCT patients were between 42 and 82 and 22 and >90, respectively. For two of the HSCT recipients, HHV-6B TRS PCR products of different sizes were detected in several isolates from each patient, which suggests mixed HHV-6B infections. In two of the posttransplant HHV-6B encephalitis patients, the sizes of the TRS nested PCR products amplified from the reactivated virus detected in the central nervous system differed from those of the virus detected in initial isolates from peripheral blood mononuclear cells. Taken together, these results suggest that PCR analysis of TRS copy number is a reliable tool for the discrimination of HHV-6B clinical isolates. Additionally, mixed HHV-6B infections occurred in HSCT recipients, and in some cases, compartmentalization of the HHV-6B strains to the central nervous system versus the blood compartment occurred in posttransplant HHV-6B encephalitis patients.

Human herpesvirus 6 (HHV-6) is the only virus known to integrate into human chromosomes and be transmitted from parents to offspring. Less than 1% of the population carries integrated HHV-6 in their genomes. Here, we report the case of a 9-year-old Japanese girl with an extraordinarily high copy number of HHV-6B in her genome. The integrated virus genome was detected by real-time polymerase chain reaction (PCR) in cerebrospinal fluid and serum during the treatment of meningoencephalitis and pneumonia caused by Mycoplasma pneumoniae infection. Furthermore, the HHV-6B genome was detected in hair follicle, plasma, and whole blood in the patient and her mother, but not in the patient's father. Fluorescence in situ hybridization revealed that the viral genome was integrated into chromosome 22. Therefore, these results emphasize the importance of screening for chromosomally integrated HHV-6 prior to starting unnecessary antiviral therapies, particularly for patients harboring HHV-6 with a high copy number. (C) 2013, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Rapid differentiation between wild-type varicella zoster virus (VZV) and Oka-vaccine (vOka) strains is important for monitoring side reactions of varicella vaccination. To develop a high-throughput molecular diagnostic method for the differentiation of wild-type VZV and vOka strains based on cycling probe technology. The primers were designed to amplify common sequences spanning a single nucleotide polymorphism (SNP) in gene 62 of VZV. DNA-RNA chimeric probes (cycling probes) were designed to detect the SNP at nucleotide 105705. The cycling probe real-time PCR assays for VZV wild-type and vOka strains specifically amplified plasmids containing target sequences that ranged between 10 and 1 x 106 copies per reaction. The inter- and intra-assay coefficients of variation were less than 5%. After initial validation studies, the clinical reliability of this method was evaluated using 38 swab samples that were collected from patients suspected of being zoster. Compared to the loop mediated isothermal amplification method, which is defined as the gold standard, cycling probe real-time PCR was highly sensitive and specific. The cycling probe real-time PCR technology is a reliable tool for differentiating between wild-type VZV and vOka strains in clinical samples. (C) 2013 Elsevier B.V. All rights reserved.

第1期(1歳)にMRワクチンと水痘ワクチンを同時接種した82名、水痘ワクチンを単独接種した43名、MRワクチンを単独接種した51名を対象に、接種前後の水痘、麻疹、風疹のウイルス抗体価を測定し、副反応を調査した。同時接種者には水痘抗原に対するELISPOTアッセイを実施すると共に、接種1年後に水痘罹患状況を調査し、未罹患者に水痘ワクチンを追加接種した。更に、同時接種者には第2期(小学校就学前)にも再び同時接種し、ウイルス抗体価を測定した。その結果、水痘、麻疹、風疹ともに抗体陽転率および平均抗体価は単独接種群と同時接種群間で有意差はなかった。水痘特異的細胞性免疫能の評価では、71.4%に細胞性免疫が獲得されていた。同時接種から1年間の水痘罹患率は11%で、未罹患者に対し接種1年後に水痘ワクチンを追加接種したところブースター効果が認められた。第2期の同時接種後も、接種前と比べ水痘抗体価の有意な上昇がみられた。特に問題となる副反応はなかった。