Takuya Yamagishi

The First Identification and Retrospective Study of Severe Fever With Thrombocytopenia Syndrome in Japan

Abstract Background. Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a novel bunyavirus reported to be endemic in central and northeastern China. This article describes the first identified patient with SFTS and a retrospective study on SFTS in Japan. Methods. Virologic and pathologic examinations were performed on the patients samples. Laboratory diagnosis of SFTS was made by isolation/genome amplification and/or the detection of anti-SFTSV immunoglobulin G antibody in sera. Physicians were alerted to the initial diagnosis and asked whether they had previously treated patients with symptoms similar to those of SFTS. Results. A female patient who died in 2012 received a diagnosis of SFTS. Ten additional patients with SFTS were then retrospectively identified. All patients were aged ≥50 years and lived in western Japan. Six cases were fatal. The ratio of males to females was 8:3. SFTSV was isolated from 8 patients. Phylogenetic analyses indicated that all of the Japanese SFTSV isolates formed a genotype independent to those from China. Most patients showed symptoms due to hemorrhage, possibly because of disseminated intravascular coagulation and/or hemophagocytosis. Conclusions. SFTS has been endemic to Japan, and SFTSV has been circulating naturally within the country.

SMB-1, a Novel Subclass B3 Metallo-β-Lactamase, Associated with ISCR1 and a Class 1 Integron, from a Carbapenem-Resistant Serratia marcescens Clinical Isolate

ABSTRACT A carbapenem-resistant Serratia marcescens strain, 10mdr148, was identified in a Japanese hospital in 2010. The carbapenem resistance of this strain was attributed to the production of a novel metallo-β-lactamase (MBL), named SMB-1 (Serratia metallo-β-lactamase). SMB-1 possessed a zinc binding motif, H(Q)XHXDH (residues 116 to 121), H196, and H263 and was categorized as a member of subclass B3 MBL. SMB-1 has 75% amino acid identity with the most closely related MBL, AMO1, of uncultured bacterium, recently identified through the metagenomic analysis of apple orchard soil. The introduction of blaSMB-1 into Escherichia coli conferred resistance to a variety of β-lactam antibiotics, penicillins, cephalosporins, and carbapenems, but not aztreonam, a resistance pattern consistent with those of other MBLs. SMB-1 demonstrated high kcat values of >500 s−1 for carbapenems, resulting in the highest hydrolyzing efficiency (kcat/Km) among the agents tested. The hydrolyzing activity of SMB-1 was well inhibited by chelating agents. The blaSMB-1 gene was located on the chromosome of S. marcescens strain 10mdr148 and at the 3′ end of the ISCR1 element in complex with a typical class 1 integron carrying aac(6′)-Ib and catB3 gene cassettes. Downstream of blaSMB-1, the second copy of the 3′conserved segment and ISCR1 were found. To our knowledge, this is the first subclass B3 MBL gene associated with an ISCR1 element identified in an Enterobacteriaceae clinical isolate. A variety of antibiotic resistance genes embedded with ISCR1 have been widely spread among Enterobacteriaceae clinical isolates, thus the further dissemination of blaSMB-1 mediated by ISCR1 transposition activity may become a future concern.

Sensitive and Specific PCR Systems for Detection of Both Chinese and Japanese Severe Fever with Thrombocytopenia Syndrome Virus Strains and Prediction of Patient Survival Based on Viral Load

ABSTRACT Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high case fatality risk and is caused by the SFTS virus (SFTSV). A retrospective study conducted after the first identification of an SFTS patient in Japan revealed that SFTS is endemic to the region, and the virus exists indigenously in Japan. Since the nucleotide sequence of Japanese SFTSV strains contains considerable differences compared with that of Chinese strains, there is an urgent need to establish a sensitive and specific method capable of detecting the Chinese and Japanese strains of SFTSV. A conventional one-step reverse transcription-PCR (RT-PCR) (cvPCR) method and a quantitative one-step RT-PCR (qPCR) method were developed to detect the SFTSV genome. Both cvPCR and qPCR detected a Chinese SFTSV strain. Forty-one of 108 Japanese patients suspected of having SFTS showed a positive reaction by cvPCR. The results from the samples of 108 Japanese patients determined by the qPCR method were in almost complete agreement with those determined by cvPCR. The analyses of the viral copy number level in the patient blood samples at the acute phase determined by qPCR in association with the patient outcome confirmed that the SFTSV RNA load in the blood of the nonsurviving patients was significantly higher than that of the surviving patients. Therefore, the cvPCR and qPCR methods developed in this study can provide a powerful means for diagnosing SFTS. In addition, the detection of the SFTSV genome level by qPCR in the blood of the patients at the acute phase may serve as an indicator to predict the outcome of SFTS.

Factors Associated with Surgical Site Infection in Colorectal Surgery: The Japan Nosocomial Infections Surveillance

OBJECTIVE Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). This study aims to assess factors associated with SSI after colorectal surgery in Japan, using a Japanese national database for HAIs. DESIGN A retrospective nationwide surveillance-based study. SETTING Japanese healthcare facilities. METHODS Data on colon and rectal surgeries performed from 2008 through 2010 were extracted from a national monitoring system for healthcare-associated infections, the Japan Nosocomial Infections Surveillance (JANIS). Factors associated with SSI after colon and rectal surgery were assessed using multivariate logistic regression. RESULTS The cumulative incidence of SSI for colon and rectal surgery was 15.0% (6,691 of 44,751) and 17.8% (3,230 of 18,187), respectively. Traditional risk factors included in the National Nosocomial Infections Surveillance (NNIS) modified risk index were significant in predicting SSI in the final model for both colon and rectal surgery. Among the additional variables routinely collected in JANIS were factors independently associated with the development of SSI, such as male sex (adjusted odds ratio [aOR], 1.20 [95% confidence interval (CI), 1.14-1.27]), ileostomy or colostomy placement (aOR, 1.13 [95% CI, 1.04-1.21]), emergency operation (aOR, 1.40 [95% CI, 1.29-1.52]), and multiple procedures (aOR, 1.22 [95% CI, 1.13-1.33]) for colon surgery as well as male sex (aOR, 1.43 [95% CI, 1.31-1.55]), ileostomy or colostomy placement (aOR, 1,63 [95% CI, 1.51-1.79]), and emergency operation (aOR, 1.43 [95% CI, 1.20-1.72]) for rectal surgery. CONCLUSIONS For colorectal operations, inclusion of additional variables routinely collected in JANIS can more accurately predict SSI risk than can the NNIS risk index alone.

Epidemiological and Clinical Features of Severe Fever with Thrombocytopenia Syndrome in Japan, 2013-2014.

Although severe fever with thrombocytopenia syndrome (SFTS) was first reported from Japan in 2013, the precise clinical features and the risk factors for SFTS have not been fully investigated in Japan. Ninety-six cases of severe fever with thrombocytopenia syndrome (SFTS) were notified through the national surveillance system between April 2013 and September 2014 in Japan. All cases were from western Japan, and 82 cases (85%) had an onset between April and August. A retrospective observational study of the notified SFTS cases was conducted to identify the clinical features and laboratory findings during the same period. Of 96 notified cases, 49 (51%) were included in this study. Most case-patients were of advanced age (median age 78 years) and were retired or unemployed, or farmers. These case-patients had a history of outdoor activity within 2 weeks before the onset of illness. The median serum C-reactive protein concentration was slightly elevated at admission. Fungal infections such as invasive aspergilosis were found in 10% of these case-patients. Hemophagocytosis was observed in 15 of the 18 case-patients (83%) whose bone marrow samples were available. Fifteen cases were fatal, giving a case-fatality proportion of 31%. The proportion of neurological abnormalities and serum concentrations of lactate dehydrogenase and aspartate aminotransferase were significantly higher in the fatal cases than in the nonfatal cases during hospitalization. Appearance of neurological abnormality may be useful for predicting the prognosis in SFTS patients.

Epidemiology of domestically acquired hepatitis E virus infection in Japan: assessment of the nationally reported surveillance data, 2007-2013

In recent years, there has been an increase in the number of reported hepatitis E virus (HEV) infections from developed countries. To describe recent trends in notification and potential risk groups and risk factors in Japan, HEV infection cases and demographic, food consumption, clinical and laboratory data reported during 2007-2013 were analysed. In total, 530 HEV infections were reported during 2007-2013. Amongst 462 domestic cases, the mean age was 56.5 years (sd 13.9) and 80.1 % were male. Forty-three cases (9.3 %) were asymptomatic, amongst which 11 were detected from blood donations. Whilst ∼50 cases were reported annually during 2007-2011, the number of reported cases increased to 121 in 2012 and 126 in 2013. The increase was characterized by a rise in the number of domestic, symptomatic cases (P = 0.05) and cases confirmed by anti-HEV IgA detection (P < 0.01). HEV genotypes G3 and G4 were consistently dominant. The major suspected source of infection was food-borne, and the major suspected foods were pig, wild boar and deer meat. The observed increase during 2012-2013 was most likely due to the coverage of the anti-HEV IgA assay by the National Health Insurance system in Japan in October 2011 and its acceptance for surveillance purposes. However, the increase was not associated with detection of asymptomatic cases. Moreover, males aged 50-69 years remained as the high-risk group, and pork and other meats continued to be the most suspected items. Our findings indicated that HEV infection is an emerging and important public health concern in Japan.

Successful control of an outbreak of GES-5 extended-spectrum β-lactamase-producing Pseudomonas aeruginosa in a long-term care facility in Japan

BACKGROUND Little is known about multidrug-resistant Pseudomonas aeruginosa (MDRP) outbreaks in long-term care facilities (LTCFs). AIM To describe an MDRP outbreak in an LTCF and to clarify risk factors for MDRP acquisition. METHODS Patients who were positive for MDRP at an LTCF from January 2013 to January 2014 were analysed. A descriptive analysis, a case-control study, and a microbiological analysis were performed. FINDINGS A total of 23 MDRP cases were identified, 16 of which were confirmed in sputum samples. Healthcare workers were observed violating hand hygiene procedures when performing oral, wound, and genital care. Nasogastric tube and oxygen mask use was associated with MDRP acquisition in the respiratory tract, which might have been confounded by poor hand hygiene. Sharing unhygienic devices, such as portable oral suction devices for oral care, and washing bottles and ointments for wound and genital care with inadequate disinfection could explain the transmission of MDRP in some cases. Isolates from 11 patients were found to be indistinguishable or closely related by pulsed-field gel electrophoresis and harbouring the blaGES-5 gene. Subsequent enhanced infection control measures were supported by nearby hospitals and a local public health centre. No additional cases were identified for a year after the last case occurred in January 2014. CONCLUSION An outbreak of MDRP with an antimicrobial resistance gene, blaGES-5, occurred in a Japanese LTCF. It was successfully controlled by enhanced infection control measures, which neighbouring hospitals and a local public health centre supported.

Ongoing increase in measles cases following importations, Japan, March 2014: times of challenge and opportunity.

WPSAR Vol 5, No 2, 2014 | doi: 10.5365/wpsar.2014.5.2.001 www.wpro.who.int/wpsar 1 a Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan. b Department of Virology 3, National Institute of Infectious Diseases, Tokyo, Japan. Submitted: 1 April 2014; Published: 16 May 2014 doi: 10.5365/wpsar.2014.5.2.001 Ongoing increase in measles cases following importations, Japan, March 2014: times of challenge and opportunity

A Case of Bilateral Adrenal and Pleural Metastases from Prostate Cancer.

Our case was 65 years old. At check-up, a high PSA level of 515 ng/ml was observed, the patient was diagnosed with having clinical stage D prostate cancer and a Maximum Androgen Blockade (MAB therapy) was started. In response to the exacerbated prostate cancer, we started a therapy involving the administration of 8 mg/kg body weight of dexamethasone and 55 mg/m2 of docetaxel every 3 weeks. After completing 8 courses, an enlargement of the bilateral adrenal tumor was observed, and after completing 12 courses, a pleural tumor was discovered and the PSA level was also increased. The patient was therefore diagnosed with having bilateral adrenal metastasis and pleural metastasis of prostate cancer through diagnostic imaging. So far, there have been no reports of multiple occurrences of prostate cancer in the adrenal glands and the pleura, thus making this case the first such case.

A Epidemiological Investigation of a Nosocomial Outbreak of Multidrug-Resistant Acinetobacter baumannii in a Critical Care Center in Japan, 2011–2012

In 2011, a multidrug-resistant Acinetobacter baumannii (MDRAB) outbreak occurred at a Japanese critical care center (CCC) in a tertiary care hospital. Multidrug-resistance in Japan is defined as resistance to the antimicrobials amikacin, carbapenem, and fluoroquinolone. We conducted a retrospective epidemiological investigation of this outbreak to identify the risk factors for MDRAB respiratory tract acquisition in this hospital. Cases were defined as hospitalized patients with MDRAB-positive cultures at least 3 days post admission to the CCC between June 1, 2011 and April 20, 2012. Fifteen MDRAB cases were identified, including 3 with infection and 12 with colonization. This case-control study demonstrated that hypoalbuminemia along with carbapenem administration were associated with MDRAB respiratory tract acquisition. Pulsed-field gel electrophoresis analysis and multilocus sequence typing using MDRAB isolates suggested a clonal dissemination of MDRAB strains with sequence type 74 occurred primarily among patients admitted to the CCC. From April 16, 2012, a decreased isolation rate of MDRAB in the hospital occurred after the implementation of the following infection control measures: closing the emergency room, discontinuing admission to the CCC, isolating patients with MDRAB colonization or infection to single room status, and conducting environmental cleaning. No MDRAB cases were detected between March 23 and April 20, 2012.