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Brain Dev 2021 May 7. Epub 2021 May 7.

Department of Neurology, Nagano Children's Hospital, Azumino, Japan. Electronic address:

Background: The most common causative pathogen of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was reported as HHV-6. Although excitotoxic injury with delayed neuronal death is considered to be a possible pathogenesis of AESD, the detailed pathophysiology remains unclear.

Case Presentation: We present a twelve-month-old girl with AESD due to HHV-6 primary infection. Read More

BMJ Paediatr Open 2021 2;5(1):e001034. Epub 2021 Apr 2.

Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.

Background: Epidemiological studies in Kawasaki disease (KD) have suggested infectious aetiology. During the COVID-19 pandemic, measures for mitigating SARS-CoV-2 transmission also suppress the circulation of other contagious microorganisms. The primary objective is to compare the number and incidence of KD before and during the COVID-19 pandemic in Japan, and the secondary objective is to investigate temporal association between the KD epidemiology and activities of SARS-CoV-2 and other viral and bacterial infections. Read More

J Pediatr Hematol Oncol 2021 Apr 6. Epub 2021 Apr 6.

Departments of Pediatric Infection Pediatrics Pediatric Hematology/Oncology, Faculty of Medicine, Koç University, İstanbul, Turkey.

Introduction: Roseola infantum is always considered to be among the differential diagnosis of young patients with fever and leukopenia whom to be strictly isolated with the preliminary diagnosis of COVID-19 until otherwise proven during the pandemic.

Results: Human herpes virus-6 (HHV-6) polymerase chain reaction (PCR) blood test was performed in 4 of 7 patients with a clinical diagnosis of roseola infantum and all found to be HHV-6 PCR positive. The most striking laboratory finding in all patients was leukopenia. Read More

Transpl Infect Dis 2020 Oct 8;22(5):e13331. Epub 2020 Jun 8.

Deprtment of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Human herpesvirus-6 (HHV-6) is a common pathogen affecting the human population. Primary HHV-6 infection generally occurs during infancy and causes exanthema subitum. Moreover, HHV-6 may exhibit inherited chromosomally integrated HHV-6 (iciHHV-6) in certain individuals. Read More

J Pediatric Infect Dis Soc 2021 Mar;10(2):175-178

Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan.

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. Read More

J Infect Chemother 2020 Mar 1;26(3):251-256. Epub 2019 Nov 1.

Department of Pediatrics, National Hospital Organization Beppu Medical Center, 1473 Oaza-Uchikamado, Beppu, Oita, 874-0011, Japan. Electronic address:

Background: This study aimed to elucidate the etiologies and diagnostic errors of early-phase pediatric fever without an obvious cause.

Methods: This single-center, retrospective, descriptive study included 1334 febrile children hospitalized at Beppu Medical Center in Japan between 2014 and 2018. Eligibility criteria were age ≤12 years, axillary temperature ≥38. Read More

Pediatr Infect Dis J 2019 10;38(10):e248-e253

Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan.

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. Read More

J Pediatr 2019 09 14;212:228-231. Epub 2019 Jun 14.

Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO; Children's Hospital Colorado, Aurora, CO.

An immunocompetent toddler came to medication attention with gastroenteritis, complicated by encephalopathy and hepatitis. Multiplexed testing using a polymerase chain reaction meningitis panel was positive for human herpesvirus 6 (HHV-6). Clinical correlation, quantitative HHV-6 polymerase chain reaction, and metagenomic next-generation sequencing supported a likely diagnosis of primary HHV-6B infection. Read More

J Dermatol 2018 Oct 27;45(10):1199-1202. Epub 2018 Jul 27.

Department of Pediatrics, Showa General Hospital, Tokyo, Japan.

Infantile hemangiomas grow rapidly during infancy followed by gradual involution. After involution, residual lesions sometimes remain. Despite the prognosis for eventual involution, infantile hemangiomas often cause great psychosocial morbidity that affects patients and their parents. Read More

J Med Virol 2018 11 13;90(11):1757-1764. Epub 2018 Aug 13.

HerpeZ, University Teaching Hospital, Lusaka, Zambia.

Background: Human herpesvirus 6B (HHV-6B) is the causative agent of Roseola infantum, and has also been suggested to play a role in the pathogenesis of febrile seizures in young children, a percentage of whom go on to develop febrile status epilepticus (FSE), but the existing data is conflicting and inconclusive. HHV-6A is a distinct species, rarely detected in most parts of the world, but prior studies suggest a higher prevalence in febrile African children. We describe a case-control study comparing the frequency of HHV-6A and/or HHV-6B infections in children with febrile seizures (including FSE) and a control group of febrile children without seizures. Read More

J Med Virol 2018 10 10;90(10):1636-1642. Epub 2018 Jul 10.

Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.

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. Read More

Neuropathology 2018 Mar 26. Epub 2018 Mar 26.

Department of Pediatrics, Oita University Faculty of Medicine, Yufu, Japan.

Human herpes virus 6 (HHV-6) is known to cause primary encephalitis in the frontal lobes/cerebral hemisphere or reactivated encephalitis in the hippocampus, but the pathogenesis remains unclear. HHV-6B has also been detected in hippocampal samples in patients with mesial temporal lobe epilepsy. A 1 year and 3 months old female, who had been clinically diagnosed with exanthema subitum and febrile convulsion, was found dead on the third day after onset. Read More

Brain Dev 2018 Mar 25;40(3):242-246. Epub 2017 Sep 25.

Department of Pediatrics, Gunma Chuo Hospital, Japan.

Introduction: The relevant literature includes several case reports on cerebral infarction in children with HHV-6 infection; however, there is no report of brain stem infarction.

Case: An 11-month-old girl was hospitalized because of fever. She was unable to stand up and meet her mother's gaze. Read More

Biochem Biophys Res Commun 2017 05 22;486(3):706-711. Epub 2017 Mar 22.

Department of Virology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan.

Human herpesvirus 6B (HHV-6B) causes exanthema subitum in infants and is known to be mildly pathogenic. However, HHV-6B infection can induce febrile seizures in a high percentage of patients, and in rare cases, result in encephalitis. We detected higher levels of interleukin (IL)-1β and basic fibroblast growth factor (bFGF) in the cerebrospinal fluid (CFS) of patients with HHV-6B encephalitis when compared to those in patients with non-HHV-6B-induced febrile seizures. Read More

J Med Virol 2017 04 27;89(4):696-702. Epub 2016 Sep 27.

Departments of Virology and Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

The amounts of the DNAs of human herpesviruses-6 (HHV-6) and -7 (HHV-7) in saliva samples were monitored during the acute and convalescent phases of exanthem subitum (ES) to elucidate the kinetics of virus shedding after ES. A total of 247 saliva samples were collected from 17 children (5 males and 12 females: 8-31 months old at onset). The monitoring period ranged from 152 to 721 days after onset, and in 15 children it was longer than 1 year. Read More

Pediatr Int 2016 May 29;58(5):415-417. Epub 2015 Dec 29.

Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan.

Enterovirus focal encephalitis is a rare clinical entity that is characterized by focal neurological signs including seizure, hemiparesis, hemichorea, and headache, which are mainly followed by rapid spontaneous improvement. We herein describe the case of a 9-month-old boy who developed Coxsackie virus B5 (CVB5) focal encephalitis with seizure clusters in the eruption stage of roseola infantum-like illness, which were followed by rapid improvement and benign outcome. Lumbar puncture indicated pleocytosis, and CVB5 infection in the cerebrospinal fluid was subsequently identified on genome sequencing and virus isolation. Read More

Brain Dev 2015 Sep 9;37(8):829-32. Epub 2015 Jan 9.

Department of Pediatrics, Asahikawa Medical University, Asahikawa 078-8510, Japan.

Background: Human herpesvirus-6 (HHV-6) is the etiological agent of exanthema subitum-associated encephalopathy, which usually occurs in children younger than 3 years. Brain imaging shows various abnormalities.

Patient: A previously healthy 4-year-old girl developed acute encephalopathy with clinical features consisting of fever, repetitive seizures, and a disturbance of consciousness. Read More

Jundishapur J Microbiol 2014 Sep 1;7(9):e11821. Epub 2013 Sep 1.

Pediatrics Medical Center, Tehran University of Medical Sciences, Tehran, IR Iran.

Background: Encephalitis is swelling and inflammation of brain, usually due to viral infection. Viral encephalitis symptoms could be fever, headache, altered level of consciousness, and seizures.

Objectives: The aim of this study was detection of human herpesvirus-6 (HHV-6) DNA in cerebrospinal fluid (CSF) of patients with symptoms of possible acute encephalitis and without typical signs or symptoms of roseola infantum, using real-time polymerase chain reaction (PCR). Read More

Curr Opin Virol 2014 Dec 14;9:91-6. Epub 2014 Oct 14.

Division of Infectious Diseases, Department of Pediatrics, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 690, Rochester, NY 14642, USA. Electronic address:

The roseoloviruses, human herpesvirus-6A -6B and -7 (HHV-6A, HHV-6B and HHV-7) cause acute infection, establish latency, and in the case of HHV-6A and HHV-6B, whole virus can integrate into the host chromosome. Primary infection with HHV-6B occurs in nearly all children and was first linked to the clinical syndrome roseola infantum. However, roseolovirus infection results in a spectrum of clinical disease, ranging from asymptomatic infection to acute febrile illnesses with severe neurologic complications and accounts for a significant portion of healthcare utilization by young children. Read More

Pediatr Neurol 2014 Sep 13;51(3):448-52. Epub 2014 Apr 13.

Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan. Electronic address:

Background: Human herpesvirus 6 is a significant cause of the febrile illness roseola infantum in young children. Infection with human herpesvirus 6 typically causes a self-limited febrile illness but occasionally is associated with central nervous system manifestations, including febrile seizures and encephalitis. Host factors associated with severe manifestations of human herpesvirus 6-associated neurological disease remain poorly characterized. Read More

J Infect Chemother 2014 Nov 21;20(11):716-21. Epub 2014 Aug 21.

Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan.

Human herpesvirus-6 (HHV-6) is a cause of exanthema subitum and, sometimes, of febrile seizures. However, the pathogenesis of febrile seizures associated with HHV-6 infection remains unclear. We investigated serum matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in infants with HHV-6 infection. Read More

Pediatr Int 2013 Apr 27;55(2):214-8. Epub 2013 Feb 27.

Department of Pediatrics, Cathay General Hospital, Taipei City, Taiwan.

Background: The aim of this study was to identify factors for differentiating roseola infantum from urinary tract infection (UTI) and to describe a cohort of infants diagnosed with roseola infantum and sterile pyuria.

Methods: The medical records of infants diagnosed with roseola infantum or UTI were examined. Multivariate analysis was performed to identify factors associated with UTI. Read More

Tohoku J Exp Med 2012 12;228(4):351-3

Department of Pediatrics, South Miyagi Medical Center, Ogawara, Japan.

Kawasaki Disease (KD) is acute, febrile, multisystem vasculitis of early childhood, the detailed mechanism of which is still unclear. Skin symptoms occur in KD, such as edema of the hands and feet with subsequent desquamation and redness at the inoculation site of bacillus Calmette-Guerin (BCG). The change at the BCG inoculation site has been considered as a specific feature of KD, although its mechanism is not fully understood. Read More

J Clin Microbiol 2012 Apr 25;50(4):1245-51. Epub 2012 Jan 25.

Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.

In order to assess the full spectrum of human herpesvirus 6A (HHV-6A)- and HHV-6B-associated diseases, we sought to develop an HHV-6 species-specific serological assay based on immunoblot analysis. The immunodominant proteins encoded by open reading frame U11, p100 for HHV-6A (strain U1102) and 101K for HHV-6B (strain Z29), were selected to generate virus species-specific antigens. Recombinant p100 and 101K were produced in a prokaryotic expression system. Read More

Pediatr Neurol 2010 Apr;42(4):277-9

Department of Pediatrics, Shiga University of Medical Science, Seta-Tsukinowa, Otsu 520-2192, Japan.

The aim of this study was to determine whether seizure susceptibility due to antihistamines is provoked in patients with febrile seizures. The study population comprised 14 patients with simple febrile seizures and 35 patients with complex febrile seizures. Detailed clinical manifestations were compared between patients with and without administration of antihistamine. Read More

Allergol Int 2010 Mar 25;59(1):83-6. Epub 2010 Nov 25.

Department of Pediatrics, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan.

Background: Drug-induced hypersensitivity syndrome (DIHS) is a rare but severe disorder due to a systemic hypersensitivity reaction. We report on a case with DIHS-like symptoms following human herpes virus 6 (HHV-6) infection complicated with encephalopathy.

Case Summary: An 11-month-old girl suffered from a human herpes virus 6 (HHV-6) infection (exanthema subitum) complicated with encephalopathy. Read More

Pediatr Neurol 2009 Nov;41(5):353-8

Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.

We sought to clarify clinical features of exanthem subitum associated-encephalitis/encephalopathy, generally caused by primary human herpesvirus-6 infection in Japan. A two-part questionnaire was sent to hospitals between January 2003-December 2004. Of 3357 questionnaires, 2357 (70. Read More

Arch Dis Child 2009 Sep 15;94(9):690-2. Epub 2009 Jun 15.

Department of Pediatrics, Assaf Harofeh Medical Center, Zerifin 70300, Israel.

Objective: To determine the aetiologies and clinical characteristics of infants with fever and a bulging fontanelle.

Design: The medical records of all febrile infants with a bulging fontanelle who underwent a lumbar puncture from January 2000 to February 2008 in Assaf Harofeh Medical Center, a university affiliated hospital in central Israel, were identified.

Results: 153 patients met the inclusion criteria. Read More

Pediatr Infect Dis J 2009 Mar;28(3):250-2

Third Department of Pediatrics, Athens University Medical School, Attikon University Hospital, Athens, Greece.

We describe the case of a 12-year-old boy with gloves and socks syndrome caused by coinfection with HHV-6 and PVB19, and review the published cases from 5 to 18 years of age to profile the disease in this age group. The review of the literature yielded 25 cases of gloves and socks syndrome. Most patients were febrile and had acute PVB19 infection. Read More

Brain Dev 2009 Nov 27;31(10):731-8. Epub 2008 Dec 27.

Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan.

Human herpesvirus-6 (HHV-6) is a causative agent of exanthema subitum. The immunological pathogenesis of acute encephalopathy associated with HHV-6 infection is still unclear. We measured the concentrations of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-4, IL-6, IL-10, and soluble TNF receptor 1 (sTNFR1) in serum and cerebrospinal fluid (CSF) during the acute stage in 15 infants with acute encephalopathy and 12 with febrile seizures associated with HHV-6 infection. Read More