Nobuhiko Okabe

Bio: Nobuhiko Okabe is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Outbreak & Vaccination. The author has an hindex of 36, co-authored 227 publications receiving 5697 citations.

Genetic Analysis of Human Norovirus Strains in Japan in 2016-2017.

Abstract: In the 2016/2017 winter season in Japan, HuNoV GII.P16-GII.2 strains (2016 strains) emerged and caused large outbreaks of acute gastroenteritis. To better understand the outbreaks, we examined the molecular evolution of the VP1 gene and RdRp region in 2016 strains from patients by studying their time-scale evolutionary phylogeny, positive/negative selection, conformational epitopes, and phylodynamics. The time-scale phylogeny suggested that the common ancestors of the 2016 strains VP1 gene and RdRp region diverged in 2006 and 1999, respectively, and that the 2016 strain was the progeny of a pre-2016 GII.2. The evolutionary rates of the VP1 gene and RdRp region were around 10-3 substitutions/site/year. Amino acid substitutions (position 341) in an epitope in the P2 domain of 2016 strains were not found in pre-2016 GII.2 strains. Bayesian skyline plot analyses showed that the effective population size of the VP1 gene in GII.2 strains was almost constant for those 50 years, although the number of patients with NoV GII.2 increased in 2016. The 2016 strain may be involved in future outbreaks in Japan and elsewhere.

Encephalitis and Encephalopathy Associated with an Influenza Epidemic in Japan

Abstract: During the winter of 1998-1999, there was an outbreak of encephalitis/encephalopathy in Japan that appeared to be associated with influenza. We conducted a national survey of the prevalence and clinical features of disease and the associated outcomes and prognostic factors related to this outbreak. A total of 202 cases were analyzed, of which 148 were diagnosed as influenza-associated encephalitis/encephalopathy on the basis of virologic analysis. Of the 148 cases studied, 130 (87.8%) were type A influenza and 17 were type B. Encephalitis/ encephalopathy developed mainly in children age <5 years, either on the day that influenza signs appeared or on the next day. The major signs included altered consciousness or loss of consciousness, convulsions, cough, and vomiting. In many patients, multiple-organ failure developed, and rates of mortality (31.8%) and disability (27.7%) were high. Thrombocytopenia and severely elevated transaminase levels were factors associated with a poor prognosis. Thus, influenza-associated encephalitislencephalopathy progressed rapidly and was associated with poor outcomes.

Hand, foot, and mouth disease caused by coxsackievirus A6, Japan, 2011.

Abstract: To the Editor: Coxsackievirus A6 (CVA6) belongs to human enterovirus species A of the genus Enterovirus. According to a Japanese Infectious Agents Surveillance Report, this virus is one of the major causes of herpangina, an acute febrile disease characterized by vesicles, ulcers, and redness around the uvula, which occurs mainly in young children and infants (1). In June 2011, a sudden increase in cases of hand, foot, and mouth disease (HFMD) at pediatric sentinel sites (≈3,000 pediatric hospitals and clinics) was reported to the National Epidemiologic Surveillance of Infectious Diseases System in Japan. Compared with past numbers of cases over 30 years of surveillance, the number of cases of HFMD per sentinel site peaked in week 28 (July) of 2011 (10.97 cases per sentinel), particularly in western Japan (2). According to the Infectious Agents Surveillance Report (as of September, 18, 2011), CVA6 was detected in 709 HFMD cases and 156 herpangina cases throughout Japan (1). Clinical samples (throat swab specimens and feces) obtained from sentinel sites in Shimane, Hyogo, Hiroshima, and Shizuoka, Japan, were screened for enteroviruses by using an enterovirus-specific reverse transcription PCR and sequence analysis of the partial viral protein (VP)4/VP2 or VP1 region (3). Among 93 clinical samples from 108 HFMD case-patients, we identified 74 case-patients as CVA6 positive by sequence analysis. On the basis of sequence analysis of the entire VP1 region (GenBank accession nos. {"type":"entrez-nucleotide-range","attrs":{"text":"AB649286-AB649291","start_term":"AB649286","end_term":"AB649291","start_term_id":"342166534","end_term_id":"342166544"}}AB649286-AB649291), the consensus sequence had 82.3%–82.5% nt identity (94.8%–95.4% aa identity) with the prototype CVA6 Gdula strain (GenBank accession no. {"type":"entrez-nucleotide","attrs":{"text":"AY421764","term_id":"40068436"}}AY421764). CVA6 was not isolated from clinical samples in a cell culture system. Therefore, most CVA6 strains were identified by molecular detection directly from clinical samples and sequence analysis. Some CVA6 strains were grown and isolated in suckling mice; these strains were antigenically identified as CVA6 by a neutralization test with specific antiserum against CVA6 (4). In Japan, HFMD and herpangina are classified as category V infectious diseases. On the basis of clinical diagnosis, suspected infections were reported by pediatric sentinel sites on a weekly basis to the Infectious Disease Surveillance Center of the National Institute of Infectious Diseases (Tokyo, Japan). Typical clinical signs and symptoms of HFMD cases caused by CVA6 were fever, mild vesicles in oral mucosa, and skin blisters on hands, arms, feet, legs, buttocks, and nail matrixes (Figure). Some patients with HFMD had onychomadesis (periodic shedding of the nails) 1–2 months after onset of HFMD. Most cases of HFMD were self-limited. However, additional follow-up may be necessary for patients with onychomadesis who are treated at dermatology clinics. Figure Typical clinical manifestations of hand, foot, and mouth disease associated with coxsackievirus CVA6 in Shizuoka, Japan, June–July, 2011. A) Hand and arm of a 2.5-year-old boy; B) foot and C) buttocks of a 6-year-old boy; D) nail matrix of a 20-month ... As in other countries in the Asia–Pacific region, major causes of HFMD in Japan were CVA16 and enterovirus 71. In 2010, enterovirus 71 was identified as a major cause of HFMD (2). In contrast, CVA6 was consistently associated with herpangina, as were CVA2, CVA4, CVA5, and CVA10, but CVA6 was occasionally detected in HFMD case-patients. CVA6 was the major cause of herpangina in 2007, but an increase in the detection rate of CVA6 in HFMD case-patients was reported in Japan in 2009 (2). HFMD outbreaks caused by CVA6 were reported in Singapore, Finland, and Taiwan in 2007–2009 (5–8). Recent HFMD outbreaks in Finland and Spain were associated with cases of onychomadesis 1–2 months after onset of HFMD (6,8,9). In Japan, cases of onychomadesis after onset of HFMD were reported in 2009 (10). Therefore, changes in clinical outcomes of CVA6-associated diseases should be investigated. Although most HFMD cases caused by CVA6 in Japan were mild, CVA6 was also detected in other clinical samples, including cerebrospinal fluid from a patient with acute encephalitis in Hiroshima, which reaffirmed possible additional clinical manifestations during an HFMD outbreak caused by CVA6. Careful surveillance of disease and infectious agent activities are crucial in monitoring CVA6-associated HFMD, onychomadesis, and neurologic diseases. Nucleotide identity between CVA6 strains in Finland (2008) (7) and Japan (2011) was ≈95% in the partial VP1 region. More detailed genetic, phenotypic, and epidemiologic analyses of CVA6 are needed to determine the role of CVA6 in HFMD outbreaks with or without onychomadesis.

Genetic analyses of GII.17 norovirus strains in diarrheal disease outbreaks from December 2014 to March 2015 in Japan reveal a novel polymerase sequence and amino acid substitutions in the capsid region.

Abstract: A novel GII.P17-GII.17 variant norovirus emerged as a major cause of norovirus outbreaks from December 2014 to March 2015 in Japan. Named Hu/GII/JP/2014/GII.P17-GII.17, this variant has a newly identified GII.P17 type RNA-dependent RNA polymerase, while the capsid sequence displays amino acid substitutions around histo-blood group antigen (HBGA) binding sites. Several variants caused by mutations in the capsid region have previously been observed in the GII.4 genotype. Monitoring the GII.17 variant's geographical spread and evolution is important. .

Enterovirus 71 from Fatal and Nonfatal Cases of Hand, Foot and Mouth Disease Epidemics in Malaysia, Japan and Taiwan in 1997-1998

Abstract: Enterovirus 71 (EV71), one of the major causative agents for hand, foot and mouth disease (HFMD), is sometimes associated with severe central nervous system diseases. In 1997, in Malaysia and Japan, and in 1998 in Taiwan, there were HFMD epidemics involving sudden deaths among young children, and EV71 was isolated from the HFMD patients, including the fatal cases. The nucleotide sequences of each EV71 isolate were determined and compared by phylogenetical analysis. EV71 strains from previously reported epidemics belonged to genotype A-1, while those from recent epidemics could be divided into two genotypes, A-2 and B. In Malaysia, genotype A-2 was more prevalent, while in Japan and Taiwan, B genotype was more prevalent. Two isolates from fatal cases in Malaysia and one isolate from a fatal case in Japan were genotype A-2. However, all isolates from three fatal cases in Taiwan belonged to genotype B. The severity of the HFMD did not link directly to certain genotypes of EV71.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

Prevention and control of influenza : recommendations of the Advisory Committee on Immunization Practices (ACIP)

Abstract: This report updates the 2002 recommendations by the Advisory Committee on Immunization Practices (ACIP) on the use of influenza vaccine and antiviral agents (CDC. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2002;51 [No. RR-3]:1-31). The 2003 recommendations include new or updated information regarding 1) the timing of influenza vaccination by age and risk group; 2) influenza vaccine for children aged 6-23 months; 3) the 2003-2004 trivalent inactivated vaccine virus strains: A/Moscow/10/99 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Hong Kong/330/2001-like antigens (for the A/Moscow/10/99 [H3N2]-like antigen, manufacturers will use the antigenically equivalent A/Panama/2007/99 [H3N2] virus, and for the B/Hong Kong/330/2001-like antigen, manufacturers will use either B/Hong Kong/330/2001 or the antigenically equivalent B/Hong Kong/1434/2002); 4) availability of certain influenza vaccine doses with reduced thimerosal content, including single 0.25 mL-dose syringes; and 5) manufacturers of influenza vaccine for the U.S. market. Although the optimal time to vaccinate against influenza is October and November, vaccination in December and later continues to be strongly recommended A link to this report and other information regarding influenza can be accessed at http://www.cdc.gov/ncidod/diseases/flu/fluvirus.htm.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection: 2009 Update by the Infectious Diseases Society of America

Abstract: These updated guidelines replace the previous management guidelines published in 2001. The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them.