A Nosocomial Outbreak Caused by Human Rhinovirus Species A Type 61 in a Welfare Facility in Gunma Prefecture, Japan.

Human rhinovirus (HRV) infections are generally referred to as the common cold, and are the main cause of mild symptoms. HRV is less frequently implicated in the development of severe respiratory infections. This study reports a nosocomial outbreak of bronchitis and pneumonia caused by HRV in a hospital during the COVID-19 epidemic in September 2022 in Gunma Prefecture, Japan. The patient continued to be symptomatic for nine days. During this outbreak, all 15 residents displayed respiratory symptoms. HRV-A was detected in 12 of the 12 samples, and phylogenetic analysis classified the strain as HRV-A type 61. HRV, COVID-19, and other respiratory infections cannot be differentiated based solely on clinical symptoms. A surveillance system to monitor them is thus needed.

Detection of Respiratory Viruses during the Early Phase of the Coronavirus Disease 2019 Pandemic in Ibaraki and Gunma Prefectures, Japan.

Respiratory infections are common, and the most common causative agent is a virus. Therefore, routine surveillance of respiratory viruses is useful in the case of novel viral diseases such as coronavirus disease 2019 (COVID-19). In this study, to clarify the kind of virus involved in suspected cases of COVID-19 in the early stages of the pandemic, we attempted to detect various respiratory viruses in 613 specimens that tested negative for severe acute respiratory syndrome coronavirus 2 using reverse transcription polymerase chain reaction. As a result, viruses were detected in 59 (9.6%) patients. In addition, human rhinovirus (HRV), human metapneumovirus (HMPV), human respiratory syncytial virus, and human parechovirus were detected in 29, 25, 3, and 2 patients, respectively. Although this study was conducted over a short period of time and not all specimens were tested, these results indicate that various respiratory viruses, especially HRV and HMPV, can be detected even during the early stages of the COVID-19 pandemic. Because various respiratory viruses maintain a constant effect during the outbreak of the newly emerged pandemic, systematic surveillance of respiratory viruses is needed during the normal period to make good use for clinical and public health.

Detailed Evolutionary Analyses of the F Gene in the Respiratory Syncytial Virus Subgroup A.

We performed evolution, phylodynamics, and reinfection-related antigenicity analyses of respiratory syncytial virus subgroup A (RSV-A) fusion (F) gene in globally collected strains (1465 strains) using authentic bioinformatics methods. The time-scaled evolutionary tree using the Bayesian Markov chain Monte Carlo method estimated that a common ancestor of the RSV-A, RSV-B, and bovine-RSV diverged at around 450 years ago, and RSV-A and RSV-B diverged around 250 years ago. Finally, the RSV-A F gene formed eight genotypes (GA1-GA7 and NA1) over the last 80 years. Phylodynamics of RSV-A F gene, including all genotype strains, increased twice in the 1990s and 2010s, while patterns of each RSV-A genotype were different. Phylogenetic distance analysis suggested that the genetic distances of the strains were relatively short (less than 0.05). No positive selection sites were estimated, while many negative selection sites were found. Moreover, the F protein 3D structure mapping and conformational epitope analysis implied that the conformational epitopes did not correspond to the neutralizing antibody binding sites of the F protein. These results suggested that the RSV-A F gene is relatively conserved, and mismatches between conformational epitopes and neutralizing antibody binding sites of the F protein are responsible for the virus reinfection.

Relationships between Viral Load and the Clinical Course of COVID-19.

To predict the clinical outcome of coronavirus disease-2019 (COVID-19), we examined relationships among epidemiological data, viral load, and disease severity. We examined viral loads of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in fatal (15 cases), symptomatic/survived (133 cases), and asymptomatic cases (138 cases) using reverse transcription quantitative real-time PCR (RT-qPCR). We examined 5768 nasopharyngeal swabs (NPS) and attempted to detect the SARS-CoV-2 genome using RT-qPCR. Among them, the viral genome was detected using the method for the 370 NPS samples with a positive rate of 6.4%. A comparison of each age showed that the fatal case was higher than the survived case and asymptomatic patients. Survived cases were older than asymptomatic patients. Notably, the viral load in the fatal cases was significantly higher than in symptomatic or asymptomatic cases (p < 0.05). These results suggested that a high viral load of the SARS-CoV-2 in elderly patients at an early stage of the disease results in a poor outcome. We should, therefore, intervene early to prevent a severe stage of the disease in such cases.

Matters of data openness and KapWeb, a web tool of multi-cancer survival analysis for cancer survivors.

KapWeb is an interactive tool for the determination of cancer survival rates based on case outcomes compiled from more than half a million records from cancer registries all over Japan, and we believe that both the tool and the call for data openness and transparency are important.

Improvement of Severe COVID-19 in an Elderly Man by Sequential Use of Antiviral Drugs.

Although a variety of existing drugs are being tested for patients with coronavirus disease 2019 (COVID-19), no efficacious treatment has been found so far, particularly for severe cases. We report successful recovery in an elderly patient with severe pneumonia requiring mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Despite administration of multiple antiviral drugs, including lopinavir/ritonavir, chloroquine, and favipiravir, the patient's condition did not improve. However, after administration of another antiviral drug, remdesivir, we were able to terminate invasive interventions, including ECMO, and subsequently obtained negative polymerase chain reaction results. Although further validation is needed, remdesivir might be effective in treating COVID-19.

Meningitis and bacteremia by nonhemolytic Group B Streptococcus strain: A whole genome analysis.

Group B streptococcus (GBS) is a leading cause of neonatal infections. Most isolates are ß-hemolytic, and their activity is considered to be pivotal for GBS pathogenicity. We report a case of a neonate with meningitis caused by nonhemolytic GBS. The patient developed meningitis 3 days after birth. Genotyping was performed and the characteristics of the strain (GCMC97051) identified by whole genome sequence using next generation sequencing. GCMC97051 possesses genetic alterations such as disruption of cylA by IS1381A insertion and a frameshift mutation in cylE, resulting in a lack of hemolysis. Thus, nonhemolytic GBS can retain the potential to cause invasive infections.

Molecular evolution of the capsid (VP1) region in human norovirus genogroup II genotype 3.

Norovirus GII.3 has been suggested to be a prevalent genotype in patients with acute gastroenteritis. However, the genetic properties of the VP1 region encoding the major GII.3 antigen remain unclear. Here, we performed molecular evolutionary analyses of the GII.3 VP1 region detected in various countries. We performed time-scaled phylogenetic analyses, selective pressure analyses, phylogenetic distance analyses, and conformational epitope analyses. The time-scaled phylogenetic tree showed that an ancestor of the GII.3 VP1 region diverged from the common ancestors of the GII.6, GII.11, GII.18, and GII.19 approximately 70 years ago with relatively low divergence. The evolutionary rate of the GII.3 VP1 region was rapid (4.82 × 10-3 substitutions/site/year). Furthermore, one positive site and many negative selection sites were observed in the capsid protein. These results suggest that the GII.3 VP1 region rapidly evolved with antigenic variations.

[The analysis of newspaper articles' reporting of legislation relating to Cancer Registries].

Objectives　The first population-based cancer registry (PBCR) was established in Japan in the 1950s; however, the legality of the registry was unclear, and scarcity of government funding resulted in data of poor quality. Although the collection of personal information is indispensable to checking for duplicated records and for patient follow-up, privacy protection was a main obstacle and was directly related to public opinion. The purpose of this study is to figure out the changing perspectives of newspaper reports about PBCR and to discuss qualitative changes in them.Methods　Articles with the PBCR-related keywords "cancer and registration", "cancer and statistics", "cancer and control policies" and "cancer and information" were extracted from five major newspapers and 50 local papers published during the 3rd-term Comprehensive 10-year Strategy for Cancer Control (2004-2013), the era of improved quality and standardization of cancer registries. From the 960 articles containing the keywords, 441 were finally for analysis.Results　Key social events occurred in the background while the articles on cancer registries increased. For instance, legislation passed for the Cancer Control Act in 2006 and the Cancer Registry Promotion Act in 2013, and carcinogenic health hazard incidents such as the nuclear plant accident after the Great East Japan Earthquake of 2011 contributed to increased interest in PBCR. The word "cancer registry" appeared most frequently in 2006 (68 times) followed by 2011 (60 times). Qualitative analysis of the articles showed the tide of public opinion turned against conservative privacy protection and toward the need for data.Conclusion　The interest in cancer registries increased during the observation period due to the background events that demanded the monitoring of cancer incidences and survival rates and providing precise information on cancer burden. For the general public, the benefit of PBCR is indirect. Active provision of information on PBCRs and related epidemiology information should help generate positive public opinion in Japanese society.

Prevalence and Risk Factor for Antibiotic-resistant Escherichia coli Colonization at Birth in Premature Infants: A Prospective Cohort Study.

BACKGROUND: Escherichia coli causes neonatal early-onset sepsis (EOS) that is associated with high mortality and increasing antibiotic resistance. Thus, we estimated the prevalence, antibiotic susceptibility and risk factors for colonization of E. coli in premature infants at birth and characterized the pathogenicity of the isolates. METHODS: A prospective surveillance study was conducted at three Japanese perinatal centers between August 2014 and February 2017. Infants weighing <2 kg and/or at gestational age <35 weeks at birth were enrolled. We screened the mothers and neonates for E. coli colonization. Pulsed-field gel electrophoresis was used to analyze the relatedness between the maternal and neonatal isolates. Virulence factors for the isolates were determined using polymerase chain reaction. RESULTS: We enrolled 421 premature infants born to 382 mothers. The rate of colonization in mothers was 47.6%, comprising 5.9% extended-spectrum beta-lactamase-producing E. coli (ESBL-E) and 20.0% ampicillin-resistant strains. Ten (2.4%) infants exhibited colonization; ESBL-E and ampicillin-resistant strains colonized three and four infants, respectively. Three antibiotic-resistant, strain-positive infants developed EOS. Pulsed-field gel electrophoresis revealed vertical transmission of bacteria in four infants. Multivariate logistic regression analysis revealed that ESBL-E-positive mothers [odds ratio (OR), 19.2; 95% confidence interval (CI), 2.5-145.7)] and vaginal delivery (OR, 9.4; 95% CI, 1.7-50.7) were risk factors for neonatal colonization. The infant isolates possessed numerous virulence factors. CONCLUSIONS: Although the prevalence of E. coli-colonized premature infants at birth was low, the rate of antibiotic resistance and the attack rate for EOS were high. Infants with ESBL-E positive mothers should be closely monitored for EOS.

Flagellum expression and swimming activity by the zoonotic pathogen Escherichia albertii.

Flagella are the well-known structural appendages used by bacteria for motility. Although generally reported to be non-motile, the enteropathogenic bacterial species Escherichia albertii produces flagella intermittently. We found that E. albertii expressed flagella under specific environmental conditions. After several generations (involving 4 to 12-h incubations), six of the twelve strains we investigated displayed swimming motility in various aquatic environments, including pond water containing nutrients from pigeon droppings (10% suspension) as well as in 20 × -diluted tryptic soy broth. The most significant motility determinant was a temperature between 15 and 30 °C. At 20 °C in the 10% pigeon-dropping suspension, microscopic observations revealed that some cells (1%-95% of six strains) showed swimming motility. Electron microscopy showed that the E. albertii cells expressed flagella. Lower concentrations of some substrates (including nutrients) may be of secondary importance for E. albertii flagella expression. Interestingly, the non-motile strains (n = 6/12) contained pseudogenes corresponding to essential flagella structural proteins. After being released from its host into surface water, E. albertii may express flagella to move toward nutrient sources or new hosts.

Next-generation DNA sequencing analysis of two Streptococcus suis ST28 isolates associated with human infective endocarditis and meningitis in Gunma, Japan: a case report.

Streptococcus suis (S. suis) is an important emerging zoonotic agent. Here, we report two cases of S. suis infection in pig farmers in Gunma Prefecture, Japan. We conducted a high-resolution molecular epidemiologic analysis on the basis of whole-genome sequencing data of each isolate using next-generation sequencing (NGS). NGS analysis revealed that the two S. suis clinical isolates were belonged to serotype 2 ST28. Phylogenetic analysis showed that two isolates were closely related to S. suis strains isolated from pigs in Japan at least until 1995. Since 41 nucleotide substitutions were found between the two strains, these strains might be derived from the same genetic lineage but distinct sporadic cases. NGS analysis is a powerful diagnostic tool for analysing bacterial infections. The database is more fulfilling, and more detailed analysis will become possible in the near future. Attention should be paid to S. suis infections, especially if the patient works on a livestock farm.

Molecular evolution of the capsid gene in human norovirus genogroup II.

Capsid protein of norovirus genogroup II (GII) plays crucial roles in host infection. Although studies on capsid gene evolution have been conducted for a few genotypes of norovirus, the molecular evolution of norovirus GII is not well understood. Here we report the molecular evolution of all GII genotypes, using various bioinformatics techniques. The time-scaled phylogenetic tree showed that the present GII strains diverged from GIV around 1630CE at a high evolutionary rate (around 10(-3) substitutions/site/year), resulting in three lineages. The GII capsid gene had large pairwise distances (maximum > 0.39). The effective population sizes of the present GII strains were large (>10(2)) for about 400 years. Positive (20) and negative (over 450) selection sites were estimated. Moreover, some linear and conformational B-cell epitopes were found in the deduced GII capsid protein. These results suggested that norovirus GII strains rapidly evolved with high divergence and adaptation to humans.

A Novel Multivariate Index for Pancreatic Cancer Detection Based On the Plasma Free Amino Acid Profile.

BACKGROUND: The incidence of pancreatic cancer (PC) continues to increase in the world, while most patients are diagnosed with advanced stages and survive <12 months. This poor prognosis is attributable to difficulty of early detection. Here we developed and evaluated a multivariate index composed of plasma free amino acids (PFAAs) for early detection of PC. METHODS: We conducted a cross-sectional study in multi-institutions in Japan. Fasting plasma samples from PC patients (n = 360), chronic pancreatitis (CP) patients (n = 28), and healthy control (HC) subjects (n = 8372) without apparent cancers who were undergoing comprehensive medical examinations were collected. Concentrations of 19 PFAAs were measured by liquid chromatography-mass spectrometry. We generated an index consisting of the following six PFAAs: serine, asparagine, isoleucine, alanine, histidine, and tryptophan as variables for discrimination in a training set (120 PC and matching 600 HC) and evaluation in a validation set (240 PC, 28 CP, and 7772 HC). RESULTS: Several amino acid concentrations in plasma were significantly altered in PC. Plasma tryptophan and histidine concentrations in PC were particularly low, while serine was particularly higher than that of HC. The area under curve (AUC) based on receiver operating characteristic (ROC) curve analysis of the resulting index to discriminate PC from HC were 0.89 [95% confidence interval (CI), 0.86-0.93] in the training set. In the validation set, AUCs based on ROC curve analysis of the PFAA index were 0.86 (95% CI, 0.84-0.89) for all PC patients versus HC subjects, 0.81 (95% CI, 0.75-0.86) for PC patients from stage IIA to IIB versus HC subjects, and 0.87 (95% CI, 0.80-0.93) for all PC patients versus CP patients. CONCLUSIONS: These findings suggest that the PFAA profile of PC was significantly different from that of HC. The PFAA index is a promising biomarker for screening and diagnosis of PC.

Understanding by the general public of newspaper reports on publicly reported cancer survival in Japan: a randomized controlled trial.

OBJECTIVE: This study was aimed to examine how well readers of newspapers understand cancer survival rate data, and the effect of this understanding on their behavioral intent. METHODS: We recruited 1950 persons who were 20 years old or older registered with a market research company. Participants were randomly divided into 10 groups; 9 were assigned one of nine newspaper articles, and the remaining group was assigned the excerpt of the official Association of Clinical Cancer Centers web pages. The primary outcome was the proportion of respondents with 'sufficient understanding', who gave 70% or more correct answers on a 10-item knowledge question. RESULTS: The proportion of participants with sufficient understanding varied across the groups (range: 0.8-22.1%, overall, P<0.001). Only around 15% of participants answered that they would consider other hospitals in a scenario where the only hospital in the participants' area had a 5-year survival of 5% or less, and answers did not significantly vary between groups (range: 11.1-21.0%, overall P=0.77). CONCLUSIONS: The level of understanding of cancer survival rate varied by variation in media reporting. However, the effect of behavioral intent on hospital choice did not differ between articles. TRIAL REGISTRATION: UMIN CTR UMIN000004885.

The significance and robustness of a plasma free amino acid (PFAA) profile-based multiplex function for detecting lung cancer.

BACKGROUND: We have recently reported on the changes in plasma free amino acid (PFAA) profiles in lung cancer patients and the efficacy of a PFAA-based, multivariate discrimination index for the early detection of lung cancer. In this study, we aimed to verify the usefulness and robustness of PFAA profiling for detecting lung cancer using new test samples. METHODS: Plasma samples were collected from 171 lung cancer patients and 3849 controls without apparent cancer. PFAA levels were measured by high-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-mass spectrometry (MS). RESULTS: High reproducibility was observed for both the change in the PFAA profiles in the lung cancer patients and the discriminating performance for lung cancer patients compared to previously reported results. Furthermore, multivariate discriminating functions obtained in previous studies clearly distinguished the lung cancer patients from the controls based on the area under the receiver-operator characteristics curve (AUC of ROC = 0.731 ~ 0.806), strongly suggesting the robustness of the methodology for clinical use. Moreover, the results suggested that the combinatorial use of this classifier and tumor markers improves the clinical performance of tumor markers. CONCLUSIONS: These findings suggest that PFAA profiling, which involves a relatively simple plasma assay and imposes a low physical burden on subjects, has great potential for improving early detection of lung cancer.

Establishing a quality measurement system for cancer care in Japan.

Ensuring the quality of care is a major objective of cancer control policy. The Cancer Control Act 2006 placed responsibility on the Japanese government to maintain the quality of cancer care nationwide. To function as centers providing high-quality care, designated cancer care hospitals (397 hospitals as of April 2012) were instituted nationwide. Although they meet the structural standards, such as the presence of radiation equipment and palliative care teams, it remains unclear whether the designation has led to appropriate provision of care and optimal patient outcomes. A national system to examine the processes and outcomes of cancer care is under development. In 2007 and 2008, the Japanese Association of Clinical Cancer Centers publicly disclosed the 5-year survival of their member facilities with strict data quality standards, including sufficient follow-up of patients' vital status. The network of designated cancer care hospitals will follow this lead to provide a national outcome monitoring system. The processes of care have also been addressed by a government-funded research project. With the collaboration of clinical experts, 206 quality indicators have been developed for five major cancers in Japan (breast, colorectal, liver, lung and stomach) and palliative care. Each indicator described the target patients and standards of care for the patients, the provision of which was considered an aspect of quality. In 2012, the Cancer Registry Chapter of the Association of Prefectural Designated Cancer Care Hospitals instituted quality measurement using these indicators. These activities will soon lead to effective quality monitoring and improvement in Japan.

Evaluation of newspaper articles for coverage of public reporting data: a case study of unadjusted cancer survival data.

The Japanese Association of Clinical Cancer Centers recently published the unadjusted 5-year survival rates of patients receiving care at each facility. A primary concern is that the media may cover this topic differently than originally intended. We examined all 13 newspaper articles that addressed the topic to assess their coverage of the public reporting program's key points, which were identified through interviews with the leader of the program. On average, 4.5 of the 10 key points identified were at least superficially covered. Although most articles mentioned the incomparability of the unadjusted data, eight created comparative tables that listed the survival data across facilities and seven sorted the facilities in descending order of survival. Four articles provided potentially misleading descriptions about the use of the relative survival. We concluded that caution is required because newspaper reports may convey potentially contradicting messages and technical details may be described inaccurately.