Publications by authors named "Tetsushi Yoshikawa"

213 Publications

Full genome-based characterization of G4P[6] rotavirus strains from diarrheic patients in Thailand: Evidence for independent porcine-to-human interspecies transmission events.

Virus Genes 2021 Jun 9. Epub 2021 Jun 9.

Department of Virology and Parasitology, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan.

The exact evolutionary patterns of human G4P[6] rotavirus strains remain to be elucidated. Such strains possess unique and strain-specific genotype constellations, raising the question of whether G4P[6] strains are primarily transmitted via independent interspecies transmission or human-to-human transmission after interspecies transmission. Two G4P[6] rotavirus strains were identified in fecal specimens from hospitalized patients with severe diarrhea in Thailand, namely, DU2014-259 (RVA/Human-wt/THA/DU2014-259/2014/G4P[6]) and PK2015-1-0001 (RVA/Human-wt/THA/PK2015-1-0001/2015/G4P[6]). Here, we analyzed the full genomes of the two human G4P[6] strains, which provided the opportunity to study and confirm their evolutionary origin. On whole genome analysis, both strains exhibited a unique Wa-like genotype constellation of G4-P[6]-I1-R1-C1-M1-A8-N1-T1-E1-H1. The NSP1 genotype A8 is commonly found in porcine rotavirus strains. Furthermore, on phylogenetic analysis, each of the 11 genes of strains DU2014-259 and PK2015-1-0001 appeared to be of porcine origin. On the other hand, the two study strains consistently formed distinct clusters for nine of the 11 gene segments (VP4, VP6, VP1-VP3, and NSP2-NSP5), strongly indicating the occurrence of independent porcine-to-human interspecies transmission events. Our observations provide important insights into the origin of zoonotic G4P[6] strains, and into the dynamic interaction between porcine and human rotavirus strains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11262-021-01851-yDOI Listing
June 2021

Sodium-containing versus sodium-trace preparations of IVIG for children with Kawasaki disease in the acute phase.

Eur J Pediatr 2021 May 10. Epub 2021 May 10.

Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan.

Kawasaki disease (KD) is an acute systemic vasculitis that most commonly causes acquired cardiac disease in children in developed countries. The most highly recommended treatment for KD is 2 g/kg intravenous immunoglobulin (IVIG). There are two types of IVIG, sodium-containing (high-Na) and sodium-trace (low-Na) preparations. However, few studies have compared the effects of these two preparations for superiority. The purpose of this study was to compare outcomes between high and low-Na IVIG preparations in KD children using a national inpatient database in Japan. We used the Diagnostic Procedure Combination database to identify KD patients treated with IVIG between 2010 and 2017. We identified those receiving high and low-Na preparations of IVIG as an initial treatment. Outcomes included proportion of coronary artery abnormalities (CAA), IVIG resistance, adverse effects, length of stay, and medical cost. Propensity score-matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results. We identified 42,345 patients with KD. There were significant differences in proportions of CAA (2.8% vs. 3.2%; p = 0.031) and IVIG resistance (17% vs. 18%, p = 0.001) between the two groups. However, there were no significant differences in length of stay or medical cost. The instrumental variable analysis confirmed the same results as the propensity score analysis.Conclusion: The present study suggests that high-Na IVIG is potentially effective for reducing the proportion of CAA in KD patients. Prospective studies are warranted to confirm the effectiveness observed in this study. What is Known: • For treatments of Kawasaki Disease in acute phase, intravenous immunoglobulin have been the most recommended to reduce fever early and prevent complications of coronary artery abnormalities. There are two types of IVIG preparations, sodium-containing IVIG and sodium-trace IVIG. However, few studies have performed comparisons to determine which preparation of IVIG is superior. What is New: • The present findings suggest that high-Na IVIG is associated with reductions in the proportions of CAAs and IVIG resistance in KD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00431-021-04096-xDOI Listing
May 2021

Hippocampal Atrophy in Pediatric Transplant Recipients with Human Herpesvirus 6B.

Microorganisms 2021 Apr 8;9(4). Epub 2021 Apr 8.

Department of Pediatrics, Fujita Health University School of Medicine, Toyoake 470-1192, Japan.

The aim of this study was to determine whether human herpesvirus 6B (HHV-6B) infection can impair the hippocampus in pediatric hematopoietic stem cell transplant (HSCT) recipients. Study subjects were pediatric HSCT recipients monitored for HHV-6B infection who underwent brain MRI before and after transplantation. Volumetric analysis of the hippocampus was performed. Of the 107 patients that received HSCT at Nagoya University Hospital Between July 2008 and April 2014, 20 were eligible for volumetric analysis. Eight patients had HHV-6B infection, of whom two had encephalopathy at the time of HHV-6B infection. None of the 12 patients without HHV-6B infection had encephalopathy. The median ratio of the right hippocampal volume from before to after transplantation was 0.93 in patients with HHV-6B infection and 1.02 in without HHV-6B infection ( = 0.007). The median ratio of the left hippocampal volume ratio in patients with and without HHV-6B infection was 0.92 and 1.00, respectively ( = 0.003). Among the eight patients with HHV-6B infection, four had a marked reduction in hippocampal volume (volume ratio < 0.90). Only one of these patients had neurological symptoms at the time of HHV-6B infection. The reduction in the hippocampal volume ratio was higher in pediatric HSCT recipients with HHV-6B infection than those without viral infection. Neurological follow-up may be required for pediatric HSCT recipients with HHV-6B infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms9040776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068176PMC
April 2021

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

Vaccine 2021 05 22;39(21):2901-2905. Epub 2021 Apr 22.

Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2021.04.009DOI Listing
May 2021

The mid-term outcome of Fontan conversion compared with primary total cavopulmonary connection.

J Cardiol 2021 Feb 26. Epub 2021 Feb 26.

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

Background: The indication of Fontan conversion (FC) from atriopulmonary connection (APC) to total cavopulmonary connection (TCPC) is unclear. We sought to analyze the mid-term outcome of prophylactic and therapeutic Fontan conversion compared with that of primary TCPC.

Methods: Patients with a univentricular heart who underwent cardiac catheterization at >18 years of age between July 2005 and July 2019 were included and divided into three groups: symptomatic APC patients who underwent therapeutic FC (t-FC, n = 13), asymptomatic APC patients after prophylactic FC (p-FC, n = 15), and patients who had primary TCPC procedure (pTCPC, n = 24).

Results: The mean last follow up was at the age of 32.0 ± 7.8, 26.8 ± 3.8, and 27.3 ± 7 years (p = 0.07) in t-FC, p-FC, and pTCPC, respectively. There was no late death. All of t-FC and 12 (80%) of p-FC cases underwent concomitant arrhythmic surgery. Consequently, five and four patients in t-FC and p-FC groups required pacemaker implantations mostly due to sinus node dysfunction. Thromboembolism was seen in 2 cases in both t-FC (15%) and p-FC (13%), and 1 case in pTCPC (4%) (p = 0.50). The last cardiac catheterization was performed at the age of 29.5 ± 8.5, 24.6 ± 3.8, and 26.3 ± 7.1 years (p = 0.11) in t-FC, p-FC, and pTCPC patients, respectively. There was no significant difference in central venous pressure, aortic pressure, and cardiac index among the three groups. There was no late supraventricular tachyarrhythmic event seen in t-FC and p-FC, whereas two patients in pTCPC had newly developed atrial flutter.

Conclusions: FC is a safe and feasible procedure to bring APC patients back onto the same track of primary TCPC patients in terms of hemodynamics as well as arrhythmia. The antiarrhythmic procedure should be carefully chosen because sinus node dysfunction can frequently occur and FC itself would reduce the risk of arrhythmia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jjcc.2021.02.005DOI Listing
February 2021

Predictors of performance on the pediatric board certification examination.

BMC Med Educ 2021 Feb 22;21(1):122. Epub 2021 Feb 22.

Center for Postgraduate Education and Training, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, Japan.

Background: Examining the predictors of summative assessment performance is important for improving educational programs and structuring appropriate learning environments for trainees. However, predictors of certification examination performance in pediatric postgraduate education have not been comprehensively investigated in Japan.

Methods: The Pediatric Board Examination database in Japan, which includes 1578 postgraduate trainees from 2015 to 2016, was analyzed. The examinations included multiple-choice questions (MCQs), case summary reports, and an interview, and the predictors for each of these components were investigated by multiple regression analysis.

Results: The number of examination attempts and the training duration were significant negative predictors of the scores for the MCQ, case summary, and interview. Employment at a community hospital or private university hospital were negative predictors of the MCQ and case summary score, respectively. Female sex and the number of academic presentations positively predicted the case summary and interview scores. The number of research publications was a positive predictor of the MCQ score, and employment at a community hospital was a positive predictor of the case summary score.

Conclusion: This study found that delayed and repeated examination taking were negative predictors, while the scholarly activity of trainees was a positive predictor, of pediatric board certification examination performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12909-021-02515-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898761PMC
February 2021

Novel ARG1 variants identified in a patient with arginase 1 deficiency.

Hum Genome Var 2021 Feb 4;8(1). Epub 2021 Feb 4.

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

We report a case of a 13-year-old boy with arginase 1 deficiency carrying a new variant in ARG1. Sanger sequencing identified the compound heterozygous variants: NM_000045.4: c.365G>A (p.Trp122*)/c.820G>A (p.Asp274Asn). Although not previously reported, the p.Asp274Asn variant is predicted to have strong pathogenicity because it is located in a highly conserved domain in the protein core and arginase activity in the patient was below measurement sensitivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41439-021-00139-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862390PMC
February 2021

An aggressive systemic mastocytosis preceded by ovarian dysgerminoma.

BMC Cancer 2020 Nov 27;20(1):1162. Epub 2020 Nov 27.

Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.

Background: Aggressive systemic mastocytosis (ASM) is a rare malignant disease characterized by disordered mast cell accumulation in various organs. We here describe a female ASM patient with a previous history of ovarian dysgerminoma.

Methods: Molecular cytogenomic analyses were performed to elucidate an etiological link between the ASM and dysgerminoma of the patient.

Results: This patient was affected by ovarian dysgerminoma which was treated by chemotherapy and surgical resection. Having subsequently been in complete remission for 2 years, she developed symptoms of ASM. A somatic D816A mutation in the KIT gene was detected in her bone marrow, which facilitated the diagnosis of ASM. Unexpectedly, this KIT D816A variant was also detected in the prior ovarian dysgerminoma sample. Whole-exome sequencing allowed us to identify a somatic nonsense mutation of the TP53 gene in the bone marrow, but not in the dysgerminoma. Microarray analysis of the patient's bone marrow revealed a copy-number-neutral loss of heterozygosity at the TP53 locus, suggestive of the homozygous nonsense mutation in the TP53 gene. In addition, the loss of heterozygosity at the TP53 locus was also detected in the dysgerminoma.

Conclusions: These results indicated that either the mast cells causing the ASM in this case had originated from the preceding ovarian dysgerminoma as a clonal evolution of a residual tumor cell, which acquired the TP53 mutation, or that both tumors developed from a common cancer stem cell carrying the KIT D816A variation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-020-07653-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693501PMC
November 2020

Effectiveness of four doses of pertussis vaccine during infancy diminished in elementary school age: A test-negative case-control study in Japan.

Vaccine 2021 01 20;39(1):11-17. Epub 2020 Nov 20.

Clinical Epidemiology Research Center, Medical Co. LTA (SOUSEIKAI), 3-5-1, Kashii-Teriha Higashi-ku, Fukuoka-city, Fukuoka 813-0017, Japan.

Objective: The Japanese national immunization program recommends that children receive 4 doses of acellular pertussis vaccine between 3 months and 2 years of age. Nevertheless, the number of pertussis cases is increasing in elementary school children aged 6-12 years. Therefore, a test-negative case-control study was conducted to assess the effectiveness of the pertussis vaccine program.

Methods: Subjects included children aged ≥3 months who visited a collaborating hospital due to pertussis-specific cough between October 2017 and November 2019. All subjects underwent diagnostic tests for pertussis, and those diagnosed as positive were regarded as cases. Subjects diagnosed as pertussis-negative were classified as controls. Vaccination history was collected using a questionnaire administered to parents with reference to immunization records. Logistic regression models were employed to calculate the odds ratio (OR) and 95% confidence interval for laboratory-confirmed pertussis.

Results: Of 187 recruited subjects (120 cases and 67 controls), questionnaire responses were obtained for 145 subjects (95 cases and 50 controls). Compared with unvaccinated subjects, the vaccine effectiveness (VE) of 4 doses was 70% among all subjects and reached to 90% with marginal significance among subjects under 6 years of age. However, among school-aged subjects, the VE was not suggestive of protection against pertussis (VE: 8%). For vaccinees given 4 doses, the OR for developing pertussis increased significantly with longer duration since the fourth dose (compared with <4.5 years, OR of 6.0-8.2 years = 5.74; OR of ≥8.3 years = 3.88; P for trend by duration < 0.01).

Conclusion: Effectiveness of administering 4 doses of pertussis vaccine during infancy decreases with time passed since the fourth dose. This regimen does not protect school-aged children against pertussis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2020.11.035DOI Listing
January 2021

Effect of a vaccine information statement (VIS) on immunization status and parental knowledge, attitudes, and beliefs regarding infant immunization in Japan.

Vaccine 2020 11 1;38(50):8049-8054. Epub 2020 Nov 1.

The Committee on Immunization and Infectious Diseases, Japan Pediatric Society, Japan; Division of Basic Nursing, Fukuoka Nursing College, Fukuoka, Japan.

Background: Because of the overabundance of vaccination information on the internet, in the media, and on social media, providing clear and correct information on immunization is critical for parental decision-making. In 2018, the Japan Pediatric Society created and distributed a Vaccine Information Statement (VIS) to provide appropriate immunization information to caregivers. The objectives of the present study were to evaluate the effect of the VIS on immunization rates, adherence to schedule, and parental understanding of immunization in Japan.

Methods: This cross-sectional study was conducted at 18 centers in 2 prefectures in Japan. Caregivers were assigned to an intervention group, which received the VIS and a questionnaire when their child reached the age of 1 month, and a control group, which received only the questionnaire. Using the self-reported questionnaires, we evaluated vaccination rates and schedule adherence at age 2 months, and parental knowledge, attitudes, and beliefs regarding immunization. Three months later, the questionnaires were returned, and the findings were compared between the 2 groups.

Results: We contacted 422 and 428 persons in the intervention and control groups, respectively, and 111/422 (26.3%) and 119/428 (27.8%) returned the surveys. Vaccination rates and adherence rates for the first dose of 4 recommended vaccines did not differ significantly (P > 0.25); however, there were some positive effects on items related to vaccine knowledge (P = 0.03), perceived benefits (P = 0.02), perceived barriers (P < 0.001), and perceived behavioral control (P = 0.01).

Conclusion: The VIS improved parent comprehension of infant immunization. Future studies should examine if the effects of such an intervention persist and affect vaccine uptake throughout childhood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2020.10.049DOI Listing
November 2020

Inherited chromosomally integrated human herpesvirus 6 and autoimmune connective tissue diseases.

J Clin Virol 2020 11 5;132:104656. Epub 2020 Oct 5.

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

Background: Entire genome of human herpesvirus 6 (HHV-6) that integrates into human chromosomes is called chromosomally integrated HHV-6 (ciHHV-6). Several viral infections have been suggested to be involved in autoimmune connective tissue diseases (CTDs). Reactivated HHV-6 from the integrated viral genome can induce immune responses against the virus. Thus, it is plausible that ciHHV-6 is associated with autoimmune CTDs.

Objectives: We sought to determine whether the prevalence of ciHHV-6 was significantly higher in patients with autoimmune CTDs than in a healthy population.

Study Design: A total of 846 peripheral blood samples collected from autoimmune CTD patients were analyzed. Since there was a large number of samples, they were pooled into 24 samples per group. Copy numbers of HHV-6 DNA were measured by real-time PCR. The threshold level for distinguishing between ciHHV-6 and active viral infection and the reliability of pooled DNA analysis were examined as initial validation experiments.

Results: The threshold level was 1.6 × 10^6 copy/mL in whole blood. The reliability of pooled DNA analysis to identify one ciHHV-6 sample among 23 HHV-6 DNA-negative samples was high. No HHV-6 DNA was detected in any of the pooled DNA samples collected from the patients. The probability of the present study including the 846 autoimmune CTD patient's samples was statistically not different with a healthy Japanese population which was 0.2 % or 0.6 %.

Conclusions: There was no significant difference in the prevalence of ciHHV-6 between a healthy population and patients with autoimmune CTDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcv.2020.104656DOI Listing
November 2020

Trend in varicella patients 4 years after implementation of universal two-dose varicella vaccination in Japan.

Vaccine 2020 10 30;38(46):7331-7336. Epub 2020 Sep 30.

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

Objective: To elucidate the trend and clinical spectrum of virologically diagnosed varicella patients after implementation of universal vaccination as a national immunization program in Japan.

Patients And Methods: Study subjects were patients suspected of varicella, less than 15 years of age, who visited 14 pediatric clinics in the Nagoya VZV Study Group from September 2015 to August 2019. Practitioners collected patient samples and information such as backgrounds, clinical symptoms, and previous immunization status. All patients were confirmed as having varicella based on molecular diagnostic assays.

Results: Varicella zoster virus (VZV) DNA was detected in swab samples from 506 (83.1%) of the 609 suspected patients. The 455 varicella patients for whom vaccination status was available were divided into two groups: 180 universal vaccination targets and 275 non-targets. Numbers of monthly varicella patients decreased gradually during the observation period. In the 2016/17 season, the seasonal epidemic of varicella became undetectable in the universal vaccination target group, and starting in the 2017/18 season, it was obscured even in the non-target group. The median age of patients was significantly lower in the universal vaccination target group (3 years) than the non-target group (7 years) (P < 0.001). Vaccination status differed significantly between the two groups (P < 0.001). Most varicella patients were in the non-target group, especially those who had been vaccinated once (60.4%). Frequency of fever (P < 0.001) and number of skin rashes at the time of the first hospital visit (P = 0.001) were significantly higher in the non-target group.

Conclusions: Although the number of childhood varicella patients declined after implementation of national immunization with two doses of varicella vaccination, sporadic outbreaks still occurred, mainly in the non-universal vaccination target group. Insufficient vaccination of members of this group is likely to be a major reason for small local outbreaks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2020.09.038DOI Listing
October 2020

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

J Infect Dis 2021 May;223(10):1717-1723

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

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiaa606DOI Listing
May 2021

Immune response against SARS-CoV-2 in pediatric patients including young infants.

J Med Virol 2021 03 29;93(3):1776-1779. Epub 2020 Sep 29.

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

Pediatric cases of the coronavirus disease 2019 (COVID-19) are generally mild or asymptomatic, and are usually detected by virological examination following close contact with COVID-19 patients, often the children's parents. The detailed clinical features and virological data of pediatric patients with COVID-19, particularly young infants, remain unclear. Here, the clinical and virological characteristics of four children with COVID-19 including two young infants were investigated. One- and 4-month-old boys with COVID-19 were both asymptomatic, and seroconversion was demonstrated. These findings suggest that even young infants can mount an immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), despite having weaker immune defenses than adolescents and adults. Three-year-old boy, who was SARS-CoV-2-negative, was admitted to the same room as his SARS-CoV-2-positive father due to the lack of caregivers. Although he was asymptomatic, he had seroconverted to SARS-CoV-2. Eleven-year-old boy, who was sibling of the 3-year-old boy, was also SARS-CoV-2-negative. He was isolated in his own room and did not seroconvert. If young children are SARS-CoV-2 negative, they should be isolated from their SARS-CoV-2-positive parents. This may be difficult in practice, if parents with COVID-19 are the only available caregivers. In such situations, the most appropriate measures should be taken for each patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.26493DOI Listing
March 2021

High-dose versus low-dose intravenous immunoglobulin for treatment of children with Kawasaki disease weighing 25 kg or more.

Eur J Pediatr 2020 Dec 29;179(12):1901-1907. Epub 2020 Aug 29.

Department of Health Policy and Informatics, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.

Little is known whether 2-g/kg IVIG is necessary for older children with Kawasaki disease (KD), because they could have more complications and financial burden. The purpose of this study was to compare outcomes between high- and low-dose IVIG in KD children with higher body weight (25 kg or more), using a national inpatient database in Japan from 2010 to 2017. We identified those receiving 2-g/kg and 1-g/kg IVIG as an initial treatment. Outcomes included the proportions of coronary artery abnormality (CAA) formation, IVIG resistance, adverse effects, length of stay, and medical costs. A propensity score matching analysis was conducted to compare the outcomes between the groups. We identified 1332 patients with KD and created 4:1 propensity score-matched pairs between high- and low-dose IVIG groups. There were no significant differences in the proportions of CAA (5.3% vs. 4.1%; p = 0.587), IVIG resistance, and length of stay. Medical costs were significantly higher in the high-dose group than in the low-dose group (p < 0.001).Conclusion: No significant difference was shown between the high- and low-dose IVIG groups in the proportions of outcomes, while medical costs were higher in the high-dose group. Further studies are needed to ascertain the appropriate IVIG dose in older patients with KD. What is Known: • For treatments of Kawasaki disease at any age in the acute phase, 2-g/kg single-dose intravenous immunoglobulin and aspirin have been the most recommended to reduce fever early and prevent complications of coronary artery abnormalities. What is New: • There was no significant difference in outcomes between children with Kawasaki disease weighing ≥ 25 kg treated with high-dose or low-dose IVIG in terms of coronary artery abnormalities, IVIG resistance, adverse effects, and length of stay, except for medical costs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00431-020-03794-2DOI Listing
December 2020

Endogenization and excision of human herpesvirus 6 in human genomes.

PLoS Genet 2020 08 10;16(8):e1008915. Epub 2020 Aug 10.

Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Sequences homologous to human herpesvirus 6 (HHV-6) are integrated within the nuclear genome of about 1% of humans, but it is not clear how this came about. It is also uncertain whether integrated HHV-6 can reactivate into an infectious virus. HHV-6 integrates into telomeres, and this has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 is located on the subtelomere of chromosome 22q (chr22q) and is required to make PIWI-interacting RNAs (piRNAs). As piRNAs block germline integration of transposons, piRNA-mediated repression of HHV-6 integration has been proposed to explain this association. In vitro, recombination of the HHV-6 genome along its terminal direct repeats (DRs) leads to excision from the telomere and viral reactivation, but the expected "solo-DR scar" has not been described in vivo. Here we screened for integrated HHV-6 in 7,485 Japanese subjects using whole-genome sequencing (WGS). Integrated HHV-6 was associated with polymorphisms on chr22q. However, in contrast to prior work, we find that the reported MOV10L1 polymorphism is physically linked to an ancient endogenous HHV-6A variant integrated into the telomere of chr22q in East Asians. Unexpectedly, an HHV-6B variant has also endogenized in chr22q; two endogenous HHV-6 variants at this locus thus account for 72% of all integrated HHV-6 in Japan. We also report human genomes carrying only one portion of the HHV-6B genome, a solo-DR, supporting in vivo excision and possible viral reactivation. Together these results explain the recently-reported association between integrated HHV-6 and MOV10L1/piRNAs, suggest potential exaptation of HHV-6 in its coevolution with human chr22q, and clarify the evolution and risk of reactivation of the only intact (non-retro)viral genome known to be present in human germlines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1008915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444522PMC
August 2020

Three Adolescents With Primary Human Herpesvirus 7 Infection During a Measles Outbreak.

Pediatr Infect Dis J 2020 08;39(8):e209-e211

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

During local small measles outbreak in Japan, 3 adolescents with febrile skin rash suspected as having measles were diagnosed with primary human herpesvirus (HHV)-7 infection. Primary HHV-7 infection can cause exanthem subitum in not only young children but also adolescents. HHV-7 should be considered as a possible causative agent for adolescent febrile skin rash during the measles outbreak.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000002697DOI Listing
August 2020

Impact of DPYD, DPYS, and UPB1 gene variations on severe drug-related toxicity in patients with cancer.

Cancer Sci 2020 Sep 20;111(9):3359-3366. Epub 2020 Jul 20.

Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.

Cancer treatment with a fluoropyrimidine (FP) is often accompanied by severe toxicity that may be dependent on the activity of catalytic enzymes encoded by the DPYD, DPYS, and UPB1 genes. Genotype-guided dose individualization of FP therapy has been proposed in western countries, but our knowledge of the relevant genetic variants in East Asian populations is presently limited. To investigate the association between these genetic variations and FP-related high toxicity in a Japanese population, we obtained blood samples from 301 patients who received this chemotherapy and sequenced the coding exons and flanking intron regions of their DPYD, DPYS, and UPB1 genes. In total, 24 single nucleotide variants (15 in DPYD, 7 in DPYS and 2 in UPB1) were identified including 3 novel variants in DPYD and 1 novel variant in DPYS. We did not find a significant association between FP-related high toxicity and each of these individual variants, although a certain trend toward significance was observed for p.Arg181Trp and p.Gln334Arg in DPYS (P = .0813 and .087). When we focused on 7 DPYD rare variants (p.Ser199Asn, p.IIe245Phe, p.Thr305Lys, p.Glu386Ter, p.Ser556Arg, p.Ala571Asp, p.Trp621Cys) which have an allele frequency of less than 0.01% in the Japanese population and are predicted to be loss-of-function mutations by in silico analysis, the group of patients who were heterozygous carriers of at least one these rare variants showed a strong association with FP-related high toxicity (P = .003). Although the availability of screening of these rare loss-of-function variants is still unknown, our data provide useful information that may help to alleviate FP-related toxicity in Japanese patients with cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cas.14553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469832PMC
September 2020

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

Microbiol Immunol 2020 Aug 4;64(8):541-555. Epub 2020 Aug 4.

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

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1348-0421.12827DOI Listing
August 2020

Rapid generation of rotavirus single-gene reassortants by means of eleven plasmid-only based reverse genetics.

J Gen Virol 2020 08 3;101(8):806-815. Epub 2020 Jun 3.

Department of Virology and Parasitology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.

Reassortment is an important mechanism in the evolution of group A rotaviruses (RVAs), yielding viruses with novel genetic and phenotypic traits. The classical methods for generating RVA reassortants with the desired genetic combinations are laborious and time-consuming because of the screening and selection processes required to isolate a desired reassortant. Taking advantage of a recently developed RVA reverse genetics system based on just 11 cloned cDNAs encoding the RVA genome (11 plasmid-only system), we prepared a panel of simian SA11-L2 virus-based single-gene reassortants, each containing 1 segment derived from human KU virus of the G1P[8] genotype. It was shown that there was no gene-specific restriction of the reassortment potential. In addition to these 11 single-gene reassortants, a triple-gene reassortant with KU-derived core-encoding VP1-3 gene segments with the SA11-L2 genetic background, which make up a virion composed of the KU-based core, and SA11-L2-based intermediate and outer layers, could also be prepared with the 11 plasmid-only system. Finally, for possible clinical application of this system, we generated a series of VP7 reassortants representing all the major human RVA G genotypes (G1-4, G9 and G12) efficiently. The preparation of each of these single-gene reassortants was achieved within just 2 weeks. Our results demonstrate that the 11 plasmid-only system allows the rapid and reliable generation of RVA single-gene reassortants, which will be useful for basic research and clinical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1099/jgv.0.001443DOI Listing
August 2020

Inherited chromosomally integrated human herpesvirus-6 in a patient with XIAP deficiency.

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. Although iciHHV-6 is generally known to be nonpathogenic, it may cause reactivation in patients with primary immunodeficiency disease (PID). XIAP deficiency is a rare PID characterized by recurrent hemophagocytic lymphohistiocytosis (HLH). It has been reported that the Epstein-Barr virus primarily causes HLH; however, the other pathogens, including HHV-6, can also cause this complication. We encountered a case of XIAP deficiency accompanied by iciHHV-6. He suffered from recurrent HLH, for which allogeneic bone marrow transplantation (BMT) was performed as a curative therapy. During the course of BMT, the patient experienced HLH three times, but there was no reactivation of endogenous HHV-6 from iciHHV-6. Finally, the patient achieved complete donor chimerism and a decline in HHV-6 DNA copy number in whole blood. This case report demonstrates no evidence of reactivation of iciHHV-6 during BMT in a patient with XIAP deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tid.13331DOI Listing
October 2020

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

Pediatr Neurol 2020 08 28;109:52-55. Epub 2020 Mar 28.

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

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pediatrneurol.2020.03.015DOI Listing
August 2020

Efficacy and safety of valganciclovir in patients with symptomatic congenital cytomegalovirus disease: Study Protocol Clinical Trial (SPIRIT Compliant).

Medicine (Baltimore) 2020 Apr;99(17):e19765

Department of Pediatrics, The University of Tokyo, Tokyo, Japan.

Background: Congenital cytomegalovirus (CMV) disease, a common mother-to-child infection, can lead to neurological sequelae. Some clinical trials have shown that oral valganciclovir (VGCV) can improve hearing and neurodevelopmental impairment in infants with congenital CMV disease. However, VGCV has neither been approved in Japan nor other countries as a treatment for this disease by the government health insurance.

Methods: This study is a non-randomized, prospective, open-label, multicenter, single-arm clinical trial and will include subjects meeting the following criteria: confirmation of positive CMV-DNA amplification in urine by an in vitro diagnostic test within 21 days of age; congenital CMV disease with one or more central nervous system disorders-microcephaly, hydrocephalus or ventricular enlargement, periventricular calcification, cortical hypoplasia or white matter injury, retinal choroiditis, and abnormal auditory brainstem response (ABR); and infants within 2 months of age with a gestational age ≥32 weeks at birth and weighing ≥1800 g at the time of registration. Subjects will be orally administered 16 mg/kg VGCV twice daily for 6 months. The target number of cases for enrollment between February 3, 2020 and July 31, 2021 is 25. Primary endpoint is the change in whole blood CMV loads before and after 6 months of treatment. The important secondary endpoint is the change in ABR (both best and total ear hearing assessments) before and after 6 months of treatment. The safety endpoints are adverse events and drug side effects.

Discussion: To the best of our knowledge, this multicenter, open-label, single-arm study will be the first well-designed clinical trial to evaluate the efficacy of oral VGCV in infants with congenital CMV diseases. The findings will reveal the efficacy and safety of oral VGCV treatments and enable the approval of oral VGCV as a treatment for infants with congenital CMV disease by the government health insurance of Japan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000019765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220768PMC
April 2020

Full genome characterization of novel DS-1-like G9P[8] rotavirus strains that have emerged in Thailand.

PLoS One 2020 22;15(4):e0231099. Epub 2020 Apr 22.

Department of Virology and Parasitology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.

The emergence and rapid spread of unusual DS-1-like intergenogroup reassortant rotaviruses having G1/3/8 genotypes have been recently reported from major parts of the world (Africa, Asia, Australia, Europe, and the Americas). During rotavirus surveillance in Thailand, three novel intergenogroup reassortant strains possessing the G9P[8] genotype (DBM2017-016, DBM2017-203, and DBM2018-291) were identified in three stool specimens from diarrheic children. In the present study, we determined and analyzed the full genomes of these three strains. On full-genomic analysis, all three strains were found to share a unique genotype constellation comprising both genogroup 1 and 2 genes: G9-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analysis demonstrated that each of the 11 genes of the three strains was closely related to that of emerging DS-1-like intergenogroup reassortant, human, and/or locally circulating human strains. Thus, the three strains were suggested to be multiple reassortants that had acquired the G9-VP7 genes from co-circulating Wa-like G9P[8] rotaviruses in the genetic background of DS-1-like intergenogroup reassortant (likely equine-like G3P[8]) strains. To our knowledge, this is the first description of emerging DS-1-like intergenogroup reassortant strains having the G9P[8] genotype. Our observations will add to the growing insights into the dynamic evolution of emerging DS-1-like intergenogroup reassortant rotaviruses through reassortment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231099PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176146PMC
July 2020

Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis.

Front Immunol 2019 26;10:2715. Epub 2019 Nov 26.

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8,742 persons with MS and 7,215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further. The IgG response against IE1A was positively associated with MS (OR = 1.55, = 9 × 10), and increased risk of future MS (OR = 2.22, = 2 × 10). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, = 6 × 10). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, = 6 × 10). The association did not differ between MS subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody responses were located to the Human Leukocyte Antigen (HLA) region and the strongest association for IE1A was the DRB113:01-DQA101:03-DQB106:03 haplotype while the main association for IE1B was DRB113:02-DQA101:02-DQB106:04. In conclusion a role for HHV-6A in MS etiology is supported by an increased serological response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2019.02715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988796PMC
November 2020

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

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jpids/piaa009DOI Listing
March 2021

Respiratory illness and acute flaccid myelitis in the Tokai district in 2018.

Pediatr Int 2020 Mar;62(3):337-340

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

Background: An outbreak of acute flaccid myelitis was chronologically correlated with an outbreak of severe respiratory illness in Japan in 2015. We hypothesized that increases in children hospitalized with severe respiratory illnesses might also be associated with increase in acute flaccid myelitis in autumn 2018.

Methods: We explored the temporal correlations between respiratory illness outbreaks and acute flaccid myelitis during autumn season between 2016 and 2018 using questionnaire surveys. One questionnaire explored the monthly numbers of children with acute flaccid myelitis, Guillain-Barré syndrome, and other acute flaccid paralyses. The other questionnaire explored the monthly numbers of children hospitalized with respiratory illnesses associated with wheezing. A correlation between the monthly numbers of children with acute flaccid myelitis and those with respiratory illness was analyzed using the Pearson correlation test.

Results: Although the number of patients hospitalized with respiratory illness did not correlate with the number of those admitted with myelitis, increases in children aged 7-12 and 13-19 years requiring intensive care unit admission correlated temporally with an outbreak of acute flaccid myelitis.

Conclusions: An increase in intensive care unit admissions to treat respiratory disease occurred in association with a cluster of acute flaccid myelitis. An increase in the number of intensive care unit admissions due to respiratory illness may be a clue to expect the occurrence of acute flaccid myelitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ped.14128DOI Listing
March 2020

Frequency of subclinical herpes zoster in pediatric hematology-oncology patients receiving chemotherapy: A retrospective cohort analysis.

J Med Virol 2020 08 18;92(8):1260-1265. Epub 2019 Dec 18.

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

Varicella-zoster virus (VZV) reactivation from the enteric nervous system can cause ileus (Ogilvie's syndrome) in adult patients. Since no pediatric cases have been described, we sought to retrospectively analyze VZV reactivation in pediatric hematology-oncology patients to determine whether VZV infection including subclinical VZV reactivation can induce gastrointestinal complications such as Ogilvie's syndrome. Thirty-five patients who received chemotherapy at our institution between September 2013 and June 2018 were included. Serum samples were collected weekly during hospitalization and every 3 months during outpatient maintenance chemotherapy. A real-time polymerase chain reaction assay was used to measure VZV DNA load in serum. The clinical features of patients with VZV infection were retrospectively analyzed. Of 1165 serum samples, 7 (0.6%) were positive for VZV DNA. VZV DNA was detected in 3 of 35 patients. In patient A, VZV DNA was detected during two episodes. The first episode involved varicella-like eruptions caused by the Oka VZV vaccine strain. The second episode involved herpes zoster (HZ) caused by the same strain. Patients B and C had a clinical course that was typical for HZ caused by wild-type VZV. No gastrointestinal symptoms were observed at the time of VZV infection in these three patients. VZV DNA was not detected in any other samples. No pediatric cases with Ogilvie's syndrome caused by VZV reactivation were demonstrated in this cohort. Additionally, no subclinical VZV reactivation was found in this cohort. Further study is needed to elucidate the precise incidence of pediatric Ogilvie's syndrome caused by VZV reactivation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.25650DOI Listing
August 2020

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

Transpl Infect Dis 2020 Feb 11;22(1):e13203. Epub 2019 Nov 11.

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

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tid.13203DOI Listing
February 2020