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Introduction: A blood culture (BC) test is vital for diagnosing bacteremia in clinical practice. Although incubation time varies among automated BC systems, 4-5 days is deemed to be sufficient time for the BD BACTEC FX blood culture system. This study compared the clinical and microbiological characteristics of true-positive BC samples on day 5 with those within 4 days to reduce missed true bacteremia cases., Methods: We conducted a retrospective study of blood cultures from hospitalized patients between April 2020 and April 2023 at a tertiary care hospital in Japan., Results: In total, 12,342 BC sets were collected from 6,567 patients. Gram-positive bacilli other than Bacillus spp. and Corynebacterium spp., non-albicans Candida, and yeasts other than Candida spp. were detected more frequently in BC-positive patients on day 5 than in those within 4 days. The gastrointestinal tract was the portal of entry more frequently on day 5 than within 4 days (25 % vs. 4 %, p = 0.006)., Conclusion: A 4-day incubation period is sufficient for the BD BACTEC FX blood culture system under routine conditions. However, a 5-day incubation period may be warranted when low pathogenicity is suspected or the gastrointestinal tract is suspected as the portal of entry., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Methylobacterium populi is a fastidious, pink-pigmented, Gram-negative bacterium that has been isolated from poplar trees that are found throughout the Northern Hemisphere in both temperate and subtropical regions. Herein, we report a novel case of M. populi peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). A 45-year-old Japanese man with a history of hypertension and chronic kidney disease was diagnosed with CAPD-associated peritonitis. After starting broad-spectrum antibiotics, white blood cell (WBC) count in the CAPD effluent remained elevated. On day 7, the CAPD effluent grew Gram-negative vacuolated rods identified as M. populi using 16S ribosomal RNA gene sequences. After the treatment regimen was changed to intraperitoneal gentamicin, the WBC count in the CAPD effluent decreased, and the clinical features improved. Although infection with M. populi is rare, clinicians should advise patients on CAPD to avoid contact with poplar trees and provide training on adherence to CAPD exchange protocols, including hand hygiene.

Background: Cefmetazole (CMZ) is a carbapenem-sparing option in the treatment of extended-spectrum beta-lactamase (ESBL)-producing bacterial infection. In this pilot study, we aimed to compare the effects of antimicrobial treatment (meropenem [MP] and CMZ) with those of no antimicrobial treatment (control group) on the microbiome., Methods: The study was a multicenter, prospective, observational pilot study conducted from October 2020 to October 2022. Feces and saliva samples were collected for microbiome analyses at two time points (early-period: days 1-3; and late-period: days 4-30) for the antimicrobial treatment group, and at one time point for the control group., Results: Five feces (MP-F and CMZ-F) and five saliva (MP-S and CMZ-S) samples were included in the MP and the CMZ groups. Ten feces (C-F) and saliva (C-S) samples were included in the control group. Group α diversity was notably lower in the late-period MP-F group than the control group as determined with the Shannon richness index. β diversity analysis of the feces samples based on weighted and unweighted UniFrac distances revealed distinctions in both the late-period CMZ-F and MP-F groups compared with the control group. Weighted UniFrac analysis showed that only the early-period MP-F group differed from the control group. In the saliva samples, weighted and unweighted UniFrac analyses showed significant differences between the control group and the early CMZ, late CMZ, and late MP groups., Conclusions: MP treatment may cause larger impact on the feces microbiome than CMZ in Japanese patients., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

The variants of concern (VOCs) of SARS-CoV-2 have exhibited different phenotypic characteristics in clinical settings which are yet to be fully explored. This study aimed to characterize the viral replication features of major VOCs of SARS-CoV-2 and their association with pathogenicity. The Alpha, Delta, and Omicron variants of SARS-CoV-2 isolated from the COVID-19 patients in Japan were propagated in VeroE6/TMPRSS2 cells. The viral replication and pathological features were evaluated by laser and electron microscopy at different time points. The results revealed that the Delta variant dominantly infected the VeroE6/TMPRSS2 cells and formed increased syncytia compared to the Alpha and Omicron variants. Relatively large numbers of virions and increased immunoreactivities of the SARS-CoV-2 N-protein were detected in the endoplasmic reticulum and intracellular vesicles of Delta-infected cells. Interestingly, the N-protein and virions were detected in the nucleus of Delta-infected cells, while such properties were not observed in the case of Alpha and Omicron variants. In addition, early nuclear membrane damage followed by severe cellular damage was prominent in Delta-infected cells. A unique mutation (G215C) in the N-protein of the Delta variant is thought to be associated with severe cell damage. In conclusion, this study highlights the distinct replicative and pathogenic characteristics of the Delta variant of SARS-CoV-2 compared to the Alpha and Omicron variants, shedding light on the potential mechanisms underlying its increased pathogenicity.

Objectives: Nipah virus (NiV), a bat-borne zoonotic pathogen, poses persistent threats to global public health due to severe clinical manifestation and high case fatality rate (CFR). A critical examination of NiV outbreaks is essential for refining strategies and mitigating the impact of future infections. In this study, we provide a concise update on global NiV outbreaks that occurred during the past 25 years., Methods: In this geospatial study, we conducted an in-depth examination of the epidemiological characteristics of human NiV cases and deaths from 1998 to 2024 through multiple analyses of public data and official reports., Results: NiV emerged in 1998 in Malaysia during an outbreak among pig farmers. Since then, NiV outbreaks have been documented in five countries of South and Southeast Asia (Bangladesh, India, Malaysia, Philippines, and Singapore). As of May 2024, there have been 754 confirmed human NiV cases with 435 deaths (CFR: 58%) reported in these five countries. Bangladesh records the highest incidence (341 cases and 241 deaths; CFR: 71%) followed by Malaysia (283 cases and 109 deaths; CFR: 39%), India (102 cases and 74 deaths; CFR: 73%), the Philippines (17 cases and nine deaths; CFR: 53%), and Singapore (11 cases and one death; CFR: 9%)., Conclusions: The clinical outcomes of NiV have been underscoring constant global public health threats as no effective therapies and vaccines are available. Strong global understandings, with an eye on developing vaccines and therapeutics, are required to minimize clinical outcomes and future threats of NiV., Competing Interests: The authors have no competing interests to declare., (© 2024 The Author(s).)

Objectives: Dengue, a life-threatening disease caused by the mosquito-borne dengue virus, has become a severe problem in recent years in Bangladesh, a South Asian country. In this study, we have critically analyzed the factors contributing to the escalation of the dengue burden in recent years in Bangladesh and discussed the strategies for effective control., Design: This retrospective observational study analyzed the dengue data collected from the five most dengue-affected countries (Bangladesh, Brazil, Mexico, Peru, and the Philippines) from 2019 to 2023., Results: An increased number of dengue-related deaths has been recorded in Bangladesh since 2021. The year 2023 has witnessed a record high dengue-related deaths in Bangladesh, with cumulative deaths for the year surpassing all totals of the previous 23 years (2000-2022: 853 deaths vs 2023: 1705 deaths). Comparing the epidemiologic data of major dengue-endemic countries over the last 5 years, Bangladesh recorded higher dengue fatality rates consecutively for 3 years. Besides the environmental and viral host factors, which are also applicable to many other dengue-endemic countries, there is concern about the failures and mismanagement of authorities to manage dengue patients properly., Conclusion: This study provided evidence that Bangladesh recorded higher dengue fatality rates in recent years. By implementing multi-pronged proactive approaches that can ensure proper prevention programs and appropriate patient management, Bangladesh or similar other countries can significantly reduce the current dengue burden and the associated deaths., Competing Interests: The authors have no competing interests to declare., (© 2024 The Author(s).)

No specific treatment has been developed for severe fever with thrombocytopenia syndrome (SFTS). However, the prognosis can improve with early plasma exchange. Therefore, rapid and accurate detection of SFTS virus is important for diagnosis and prognosis. Direct real-time reverse transcription polymerase chain reaction (RT-PCR) testing is easier and more time-efficient than conventional real-time RT-PCR. Our study compared direct real-time RT-PCR efficiency without the RNA extraction and purification of conventional real-time RT-PCR. Samples were collected from 18 patients with SFTS and five without SFTS. A strong correlation (r = 0.774, 95% CI: 0.652-0.857, P <0.01) was found between conventional and direct real-time RT-PCR assays. Direct real-time RT-PCR showed 84.4% sensitivity and 92.0% specificity for viral detection. Direct real-time RT-PCR is an effective diagnostic tool for patients with acute phase SFTS, but further optimization is required for viral detection.

Children infected with SARS-CoV-2 are often asymptomatic or have mild symptoms. The studies on the seroprevalence kinetics of SARS-CoV-2 antibodies in children are limited. We conducted a cross-sectional survey of the positive rate of the SARS-CoV-2 IgG in pediatric patients without suspected COVID-19 infection between January 2007 and March 2022. We defined the serum samples from the pre-pandemic and pandemic groups (1st-6th waves). Totally, 2557 samples were collected and no samples from the pre-pandemic group or the 1st-4th waves were positive for IgG. There were 4/661 and 16/373 positives at the 5th and 6th waves, respectively. At the 5th wave, the prevalence of IgG was 1.3% in children aged 1-4 years. At the 6th wave, in children <1 year of age, the prevalence was 4.0%, and 2.4%, 5.3%, 5.2% and 10% in age groups 1-4, 5-9, 10-14 and 15-18 years, respectively. In conclusions, the pre-pandemic samples were negative, and the IgG positivity increased during the later period of the pandemic., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest to declare., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Yersinia enterocolitica is a gram-negative zoonotic bacterial pathogen that is typically transmitted via the fecal-oral route. The most common clinical manifestation of a Y. enterocolitica infection is self-limited gastroenteritis. Although various extraintestinal manifestations of Y. enterocolitica infection have been reported, there are no reports of thyroid abscesses., Case Presentation: An 89-year-old Japanese man with follicular adenoma of the left thyroid gland was admitted to our hospital with a 2-day history of fever and left neck pain. Laboratory tests revealed low levels of thyroid stimulating hormone and elevated levels of free thyroxine 4. Contrast-enhanced computed tomography showed low-attenuation areas with peripheral enhancement in the left thyroid gland. He was diagnosed with thyroid abscess and thyrotoxicosis, and treatment with intravenous piperacillin-tazobactam was initiated after collecting blood, drainage fluid, and stool samples. The isolated Gram-negative rod bacteria from blood and drainage fluid cultures was confirmed to be Y. enterocolitica. He was diagnosed with thyroid abscess and thyrotoxicosis due to be Y. enterocolitica subsp. palearctica. The piperacillin-tazobactam was replaced with levofloxacin., Conclusion: We report a novel case of a thyroid abscess associated with thyrotoxicosis caused by Y. enterocolitica subsp. palearctica in a patient with a follicular thyroid adenoma., (© 2024. The Author(s).)

Patients with hematological malignancies (HM) often receive tazobactam/piperacillin (TAZ/PIPC) and glycopeptide antibiotics for febrile neutropenia. The effect of concomitant use of TAZ/PIPC on risk of teicoplanin (TEIC)-associated acute kidney injury (AKI) remains unclear. We investigated the impact of concomitant TAZ/PIPC use on TEIC-associated AKI in HM patients and identified the risk factors. In this retrospective, single-center, observational cohort study, 203 patients received TEIC, 176 of whom satisfied the selection criteria and were divided into TEIC cohort (no TAZ/PIPC; n = 118) and TEIC + TAZ/PIPC cohort (n = 58). AKI was defined as serum creatinine increase ≥0.3 mg/dL within 48 h or ≥50% from baseline. Incidence of AKI in TEIC cohort before and after propensity score matching was 9.3 and 5.9%, respectively, and that in TEIC + TAZ/PIPC cohort was 10.3 and 11.8%. AKI incidence and risk were not significantly different between two cohorts before (p = 0.829; odds ratio (OR) 1.122, 95% confidence interval (CI) 0.393-3.202) and after matching (p = 0.244; OR 2.133, 95% CI 0.503-9.043). Logistic regression analysis with factors clinically or mechanistically potentially related to TEIC-associated AKI, including concomitant TAZ/PIPC use, as independent variables identified baseline hemoglobin level as the only significant risk factor for TEIC-associated AKI (p = 0.011; OR 0.484, 95% CI 0.276-0.848). In HM patients treated with TEIC, concomitant TAZ/PIPC use did not increase AKI risk whereas lower hemoglobin levels had higher risk for TEIC-associated AKI development, suggesting the necessity to monitor serum creatinine when using TEIC in patients with anemia.

Cefmetazole is active against extended-spectrum β-lactamase-producing Escherichia coli (ESBLEC) and is a potential candidate for carbapenem-sparing therapy. This multicenter, observational study included patients hospitalized for invasive urinary tract infection due to ESBLEC between March 2020 and November 2021 at 10 facilities in Japan, for whom either cefmetazole or meropenem was initiated as a definitive therapy within 96 h of culture collection and continued for at least 3 d. Outcomes included clinical and microbiological effectiveness, recurrence within 28 d, and all-cause mortality (14 d, 30 d, in-hospital). Outcomes were adjusted for the inverse probability of propensity scores for receiving cefmetazole or meropenem. Eighty-one and forty-six patients were included in the cefmetazole and meropenem groups, respectively. Bacteremia accounted for 43% of the cefmetazole group, and 59% of the meropenem group. The crude clinical effectiveness, 14 d, 30 d, and in-hospital mortality for patients in the cefmetazole and meropenem groups were 96.1% vs 90.9%, 0% vs 2.3%, 0% vs 12.5%, and 2.6% vs 13.3%, respectively. After propensity score adjustment, clinical effectiveness, the risk of in-hospital mortality, and the risk of recurrence were similar between the two groups ( P = 0.54, P = 0.10, and P = 0.79, respectively). In all cases with available data (cefmetazole : n = 61, meropenem : n = 22), both drugs were microbiologically effective. In all isolates, bla CTX-M was detected as the extended-spectrum β-lactamase gene. The predominant CTX-M subtype was CTX-M-27 (47.6%). Cefmetazole showed clinical and bacteriological effectiveness comparable to meropenem against invasive urinary tract infection due to ESBLECs., Competing Interests: The authors declare no conflict of interest.

Background: Data on the perceptions of medical students on international experience in non-English-speaking high-income countries (HICs) are very limited. This study aimed to assess the perceptions of medical students in Japan toward overseas experience while in school and post-graduation, as well as to characterize the support they require to pursue their profession in international settings., Methods: A cross-sectional national survey was administered online between September 16, 2020, and October 8, 2020. Participants were recruited from 69 medical schools using snowball sampling through acquaintances and social media platforms. The survey results were analyzed by two researchers., Results: A total of 548 students from 59 medical schools responded to the survey. Among them, 381 respondents (69%) expressed interest in working abroad, while only 40% seriously considered it. The majority of students responded that they would like to pursue clinical training abroad for a short term or while they were medical students (54%) or during a residency/fellowship (53%). The most popular regions among the respondents for future international experiences were North America and Europe. Finally, the most reported reasons for hesitation to work abroad were language barriers (70%), followed by lack of clarity regarding career options after working abroad (67%), difficulties obtaining medical licensure abroad (62%), and the lack of role models (42%)., Conclusions: Although nearly 70% of participants reported a high interest in working overseas, various barriers to working abroad were identified. Our findings identified key problem areas that could be targeted when promoting international experiences for medical students in Japan., (© 2023. The Author(s).)

Background: The Philippines is ranked among the top countries with 200-300 annual deaths due to rabies. Most human rabies cases have been reported in remote areas, where dog surveillance is inadequate. Therefore, a strategy to effectively improve surveillance in remote areas will increase the number of detections. Detecting pathogens using portable real-time reverse transcription-polymerase chain reaction (RT-PCR) has the potential to be accepted in these areas. Thus, we aimed to develop an assay to detect the rabies virus (RABV) genome by combining the robust primer system LN34 with the PicoGene PCR1100 portable rapid instrument targeting RABV RNA (PCR1100 assay)., Methods: Procedures were optimised using an LN34 primer/probe set, KAPA3G Plant PCR Kit (KAPA Biosystems), FastGene Scriptase II (NIPPON Genetics), and an artificial positive control RNA., Results: Positive control RNA showed an analytical limit of detection of 10 copies/µL without false positivity, generating results in approximately 32 min. Compared to dFAT or RT-qPCR using field samples, the sensitivity and specificity of the PCR1100 assay were 100%, and even lower copy numbers (approximately 10 copies/µL) were detected., Conclusions: This study demonstrated that the developed assay can detect rabies RNA in field samples. Because dog-mediated rabies is endemic in remote areas, the rapidity, mobility, and practicality of the PCR1100 assay as well as the high sensitivity of the LN34 system make it an ideal tool for the confirmation of rabies in these areas., (© 2023. The Author(s).)

Introduction: Bacteroides spp. are the most common anaerobic bacteria isolated from the human gastrointestinal tract. Several resistant genes are present in Bacteroides spp. However, most studies have focused on the prevalence of the cfiA gene in Bacteroides fragilis alone. We assessed the susceptibility to antimicrobial agents and the prevalence of cepA, cfiA, cfxA, ermF, nim, and tetQ genes in Bacteroides strains isolated from clinical specimens in our hospital., Methods: We isolated 86 B. fragilis and 58 non-fragilis Bacteroides strains from human clinical specimens collected from January 2011 to November 2021. Resistance against piperacillin (PIPC), cefotaxime (CTX), cefepime (CFPM), meropenem (MEPM), clindamycin, and minocycline was determined., Results: The resistant rates of penicillins and cephalosporins in non-fragilis isolates were significantly higher than those in B. fragilis isolates. In B. fragilis isolates, the resistant rates of PIPC, CTX, and CFPM in cfxA-positive isolates were significantly higher than those in cfxA-negative isolates (71% vs. 16%, 77% vs. 19%, and 77% vs. 30%, respectively). Thirteen B. fragilis isolates harbored the cfiA gene, two of which were resistant to MEPM. Six of the 13 cfiA-positive B. fragilis isolates were heterogeneously resistant to MEPM., Conclusion: It is important to evaluate the use of MEPM as empirical therapy for Bacteroides spp. infections, considering the emergence of carbapenem resistance during treatment, existence of MEPM-resistant strains, and heterogeneous resistance., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Several cases of severe hyponatremia induced by linezolid (LZD) were reported. However, severe infections could also cause hyponatremia by increasing vasopressin secretion. To prove that hyponatremia is associated with LZD rather than infection, we compared the incidence and risk of developing hyponatremia between patients receiving LZD and those receiving vancomycin (VCM). A retrospective, single-center, observational cohort study was conducted in patients aged 18 years or older who received intravenous LZD or VCM for 7 d or longer. Hyponatremia was defined as serum sodium level lower than 134 mEq/L and more than 5% decrease from baseline after treatment initiation. The incidence and risk of developing hyponatremia were analyzed between LZD and VCM groups using chi-square test. Four hundred and fifty patients who satisfied the selection criteria were divided into LZD (n = 97) and VCM groups (n = 353). Significant differences in patient characteristics between LZD and VCM groups were observed before propensity score matching, but no significant differences were found after matching. LZD group showed a significantly higher incidence and risk of developing hyponatremia compared to VCM group both before (LZD: 16.5%, VCM: 5.4%; p < 0.001, odds ratio 3.472 [95% confidence interval (CI) 1.711-7.048]) and after (LZD: 17.8%, VCM: 5.5%; p = 0.020, odds ratio 3.738 [95% CI 1.157-12.076]) propensity score matching. In conclusion, propensity score analyses suggest that the risk of hyponatremia associated with LZD is approximately 3.7-fold higher than that associated with VCM, regardless of patient background.

The outbreak of coronavirus disease 2019 (COVID-19) devastated the overall health management strategy of most countries. In this scenario, the present study provided insights into the possible impact of the COVID-19 pandemic on dengue infection. This ecological study retrieved data from WHO/Government reporting system from 22 major dengue epidemic countries. Incidence of dengue infections during the pre-COVID-19 time (2015~2019) and COVID-19 period (2020~2021) was compared. A correlation between the dengue and COVID-19 cases and predicted dengue incidence in 2022 was calculated using the linear regression equation. Data indicated that dengue incidences across the studied area decreased by 16% during the pandemic period (2.73 million vs. 2.29 million; p < 0.05) than the same reported in pre-COVID-19 time. Although countries in Latin America reported more cases than Asia, a positive correlation (r = 0.83) between dengue and COVID-19 cases was observed in Asia. Prediction analysis warned that specific preparation for dengue management is needed in some countries of both regions in 2022 to contain the upsurge in incidences. Due to the similar nature of symptoms of dengue and COVID-19, a state of confusion will be prevailing during the ongoing pandemic. Therefore, comprehensive and evidence-based scientific approaches were warranted at all levels.

We report a case of pneumocystis pneumonia (PCP) that mimicked atypical pneumonia in a patient with human immunodeficiency virus (HIV) infection. A 44-year-old Japanese man with persistent fever and dyspnea for a month was diagnosed with atypical pneumonia because of bilateral ground-glass opacities on chest computed tomography (CT). Ground-glass opacities on chest CT diminished with three days treatment of azithromycin; however, his symptoms were persistent. Final diagnosis of HIV and PCP infection was eventually confirmed. Physicians should consider the possibility of PCP even when pulmonary manifestations resolve with azithromycin in patients with HIV infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Hashimoto et al.)

Background: Febrile neutropenia promotes renal drug excretion. Adult and pediatric patients with febrile neutropenia exhibit a lower vancomycin concentration/dose (relative to bodyweight) ratio than those with other infections. In pediatric patients, renal function relative to bodyweight varies depending on age, and vancomycin clearance is age dependent. This study aimed to analyze the effects of febrile neutropenia on the pharmacokinetics of vancomycin in age-stratified pediatric patients., Methods: This retrospective, single-center, observational cohort study analyzed 112 hospitalized pediatric patients who met the selection criteria and intravenously received vancomycin at the Department of Pediatrics of the Oita University Hospital between April 2011 and October 2019., Results: The febrile neutropenia (n = 46) cohort exhibited a significantly higher estimated glomerular filtration rate than the nonfebrile neutropenia (n = 66) cohort. Compared with those in the nonfebrile neutropenia cohort, the daily vancomycin dose relative to bodyweight and vancomycin clearance were significantly higher, and the vancomycin trough concentration and vancomycin concentration/dose ratio were significantly lower in the febrile neutropenia cohort. In the age groups of 1-6 and 7-12 years, compared with those in the nonfebrile neutropenia cohort, the vancomycin concentration/dose ratio was significantly lower, and vancomycin clearance was significantly higher in the febrile neutropenia cohort. Univariate and multivariate analyses identified febrile neutropenia as the independent factor influencing vancomycin concentration/dose ratio and clearance only in pediatric patients aged 1-6 years., Conclusions: Increased initial dosage and therapeutic drug monitoring-guided dose optimization are critical for the therapeutic efficacy of vancomycin in pediatric patients with febrile neutropenia, especially in those aged 1-6 years., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

We report a case of Campylobacter lari vertebral osteomyelitis with iliopsoas abscess. This is the first case report of vertebral osteomyelitis due to C. lari, which was identified from a vertebral biopsy sample collected using CT-guided percutaneous needle biopsy in a patient without obvious episodes of immunodeficiency. Cultureing using the HK semisolid medium aided in pathogen ideutification. It is important to make every possible effort to identify the causative pathogen in vertebral osteomyelitis.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging life-threatening infectious disease caused by the tickborne SFTS virus (SFTSV), first identified in China in 2009 and then in Japan in 2013. Human SFTS cases were reported to be concentrated in western Japan, but the epidemiological conditions of SFTSV infection in a specific region are still obscure. We performed an epidemiological study of SFTSV in Oita Prefecture on the island of Kyushu, located in western Japan. For our research, we collected sera from wild and domestic animals (deer, wild boars, raccoons, cats, and dogs) and ticks from January 2010 to November 2020 in Oita. The anti-SFTSV antibody positivity rate of deer in 2014 was significantly higher than that in 2011 (65% versus 27%, P < 0.001). The anti-SFTSV antibody positivity rates of deer, wild boars, raccoons, wild dogs, domestic dogs, and domestic cats were 55%, 12%, 27%, 1.8%, 0.53%, and 1.4%, respectively. Moreover, RT-PCR could not detect SFTSV in any tick sample. Of the six areas of Oita Prefecture, only the Eastern area showed no incidence or possibility of SFTSV infection among wild and domestic animals, ticks, and human beings. Further investigation is required to assess whether local seroepidemiology in animals will help assess the risk of SFTSV infections in inhabitants.

The pharmacokinetics of voriconazole shows large intra-individual and inter-individual variability and is affected by various factors. Recently, inflammation has been focused as a significant factor affecting the variability. This study aimed to compare the influence of C-reactive protein (CRP) and other clinical laboratory parameters on intra-individual variability in trough voriconazole concentration and examine the impact of inflammation in patients with hematological malignancies. We conducted a retrospective, single-center, observational cohort study. Forty-two patients with hematological malignancy who received oral voriconazole for prophylaxis against deep mycosis and underwent multiple measurements of trough plasma voriconazole concentration were recruited. Quantitative changes in pharmacological and clinical laboratory parameters (Δ) were calculated as the difference between the current and preceding measurements. Voriconazole concentration/maintenance dose per weight (C/D) was found to correlate positively with CRP level (n = 202, rs = 0.314, p < 0.001). Furthermore, ΔC/D correlated positively with ΔCRP level (n = 160, rs = 0.442, p < 0.001), and ΔCRP showed the highest correlation coefficient among the laboratory parameters. Univariate and multivariate analyses identified ΔCRP (p < 0.001) and Δgamma-glutamyl transpeptidase (γGTP) (p = 0.019) as independent factors associated with ΔC/D. Partial R 2 were 0.315 for ΔCRP and 0.024 for ΔγGTP, suggesting markedly greater contribution of ΔCRP to ΔC/D. In conclusion, since clinical laboratory parameters other than CRP had little influence on trough plasma voriconazole concentration, therapeutic drug monitoring and dose adjustment considering fluctuation in CRP level would be important for proper use of voriconazole in patients with hematological malignancies.

We herein report a case of presumed septic shock due to Actinotignum schaalii bacteremia with urinary tract infection. A 65-year-old Japanese man suffering from a fever was diagnosed with septic shock due to urinary tract infection. A urine sample was additionally incubated under 5% CO 2 and anaerobic conditions after A. schaalii was identified in a blood culture, but A. schaalii was not detected in the urine culture. If Gram-positive rods are observed on Gram staining of a urine sample in symptomatic patients with a predisposing urogenital condition, 5% CO 2 and an anaerobic culture of a urine sample should be performed immediately.

Blood culture tests have a major role in rapid and accurate diagnosis and selection of optimal antibiotic treatment for infectious diseases. The true-positive and contamination rates of blood cultures are performance indicators for the practice of blood culture. However, the optimal number of blood cultures has not been adequately elucidated. We aimed to assess the validity of the number of blood cultures obtained in the hospital. We conducted a retrospective study of blood cultures collected from hospitalized patients between 2010 and 2014 at a tertiary care hospital in Japan and assessed the validity of the number of blood cultures per 1,000 admissions as an indicator for the optimal practice of obtaining blood culture, considering the average length of stay. We also investigated the validity of true-positive and contamination rates of blood cultures in the hospital. The number of blood cultures in this study ranged from 28.6 to 56 per 1,000 patient-days and from 404.4 to 894.6 per 1,000 admissions. The median true-positive and contamination rates of blood cultures per year was 10.1% and 2.8%, respectively. The median contamination rate of blood cultures in a community-acquired group was significantly higher than that in a hospital-acquired group (4.1% vs. 1.9%, p = 0.029). We conclude that there is a possibility that the number of blood cultures per 1,000 admissions is a more appropriate factor to evaluate than per patient-days. Moreover, the true-positive and contamination rates of blood cultures in our hospital are valid.

Background: Yersinia pseudotuberculosis infection can occur in an immunocompromised host. Although rare, bacteremia due to Y. pseudotuberculosis may also occur in immunocompetent hosts. The prognosis and therapeutic strategy, especially for immunocompetent patients with Y. pseudotuberculosis bacteremia, however, remains unknown., Case Presentation: A 38-year-old Japanese man with a mood disorder presented to our hospital with fever and diarrhea. Chest computed tomography revealed consolidation in the right upper lobe with air bronchograms. He was diagnosed with pneumonia, and treatment with intravenous ceftriaxone and azithromycin was initiated. The ceftriaxone was replaced with doripenem and the azithromycin was discontinued following the detection of Gram-negative rod bacteria in 2 sets of blood culture tests. The isolated Gram-negative rod bacteria were confirmed to be Y. pseudotuberculosis. Thereafter, he developed septic shock. Doripenem was switched to cefmetazole, which was continued for 14 days. He recovered without relapse., Conclusions: We herein report a case of septic shock due to Y. pseudotuberculosis infection in an adult immunocompetent patient. The appropriate microorganism tests and antibiotic therapy are necessary to treat patients with Y. pseudotuberculosis bacteremia.

We herein report a case of primary sternal osteomyelitis caused by polymicrobial bacteria, including Actinomyces israelii . A 72-year-old man presented with a fever and precordial pain. Chest computed tomography (CT) revealed peristernal fluid associated with an osteolytic lesion and a peripheral nodule in the right upper lobe. We suspected sternal osteomyelitis, and an incision and drainage were performed. Culture of the drainage fluid and bone tissue yielded A. israelii , Fusobacterium necrophorum , and Streptococcus constellatus . Treatment with benzylpenicillin potassium (PCG) was administered. A subsequent chest CT scan showed that the peripheral nodule decreased in size after antimicrobial therapy. We therefore presumed the peripheral nodule as septic pulmonary embolism(SPE). Antimicrobial agents were administered for a total of 6 months. To our knowledge, this is the first case report of primary sternal osteomyelitis associated with presumed SPE caused by polymicrobial bacteria, including A. israelii . It is important to identify the causative pathogen in osteomyelitis, which requires long-term antibiotic treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Saddle pulmonary embolism (PE) and paradoxical embolism (PDE) are life-threatening disorders carrying a risk of sudden death, and their prompt diagnosis is extremely important. Saddle PE is a radiologic definition and refers to a thrombus that straddles the bifurcation of the pulmonary artery trunk, carrying a risk of sudden hemodynamic collapse. PDE is defined as a systemic arterial embolus due to the passage of a venous thrombus though a right-to-left shunt, such as patent foramen ovale (PFO). We herein present the rare case of asthma exacerbation coincident with saddle PE and PDE. A 69-year-old woman with asthma was suffering from dyspnea, pulse attenuation of the left radial artery and left upper limb pain. An arterial blood gas analysis revealed hypoxemia, and a pulmonary function test demonstrated an obstructive pattern. Enhanced computed tomography (CT) revealed saddle PE, right popliteal venous thrombosis, and left brachial artery occlusion. After the treatment with edoxaban, an anticoagulant, and aspirin, the PE was significantly alleviated, and the brachial artery occlusion was recanalized. Subsequently, the right-to-left shunt through PFO was confirmed, and PDE was suspected of inducting her brachial artery embolism. In the present case, the pulse attenuation of the radial artery and upper limb pain prompted us to consider peripheral vascular disease or coagulation disorders. Physicians should keep in mind that patients with asthma are at considerable risk of PE, and it is important to be aware of possible PFO in patients presenting with the coexistence of PE and systemic arterial embolism.

Purpose: Recent data suggest an association between Fusobacterium necrophorum infection and pharyngotonsillitis among adolescents and adults. However, existing reports are only from North America and Europe. We aimed to identify and compare the prevalence of F. necrophorum among patients with pharyngitis and asymptomatic controls in Japan and clarify the epidemiological characteristics of pharyngitis., Methods: Patients aged ≥16 years with pharyngitis and asymptomatic controls were prospectively included. F. necrophorum was detected by using both conventional culture methods and real-time F. necrophorum-specific PCR targeting the rpoB gene. The prevalence of β-hemolytic streptococci was also identified and compared between groups., Results: Forty-four pharyngitis patients and 31 asymptomatic controls were included. F. necrophorum was identified using PCR in 6 (13.6%) pharyngitis cases and 2 (6.5%) controls, with no significant difference (p = 0.457). The median bacterial load of F. necrophorum identified with real-time PCR was significantly higher in pharyngitis cases than in controls (p = 0.046). Patients with a high Centor Score tended to have a higher bacterial load than those with a low Centor Score and controls. In cases of pharyngitis, the prevalence of F. necrophorum was similar to that of Streptococcus pyogenes (F. necrophorum-positive: 6 [13.6%] vs. S. pyogenes-positive: 5 [11.4%], p = 0.99)., Conclusion: F. necrophorum was similarly prevalent among pharyngitis cases as S. pyogenes in Japan. The association of higher F. necrophorum bacterial load with symptomatic pharyngitis in accordance with the previous findings from a different geographical region suggests that F. necrophorum is an important causative agent of bacterial pharyngitis., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We herein report a case of Vibrio furnissii bacteremia with bilateral lower limb cellulitis. A 53-year-old Japanese man with a mood disorder presented to our hospital with fever and a complaint of an inability to walk. Two sets of blood cultures became positive for V. furnissii. The treatment regimen was modified to ceftazidime and doxycycline. The patient recovered without relapse. Despite thorough examinations, portal of entry of V. furnissii remained unclear. Although the bacteria was first misidentified as V. fluvialis by the phenotyping assay (API rapid ID 32E) and matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry, it was later confirmed as V. furnissii by dnaJ gene sequencing., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Dengue fever remains underreported in Africa due to a lack of awareness among healthcare providers, the presence of other febrile illnesses, and insufficient laboratory testing. We present a case of dengue fever imported from Burkina Faso to Japan, where an outbreak of dengue was reported on October 18, 2016. Phylogenetic analysis revealed that the isolate from our patient belonged to a distinct cluster of sylvatic dengue viruses, suggesting that dengue viruses have been maintained in mosquitoes and human cycles in Burkina Faso for more than 30 years.

We report a case of Zika virus infection that was imported to Japan by a traveler returning from Vietnam. We detected Zika virus RNA in the patient's saliva, urine, and whole blood. In the Zika virus strain isolated from the urine, we found clearly smaller plaques than in previous strains.

There is no proven alternative to penicillin for treatment of maternal syphilis. We report 2 case-patients with maternal syphilis who were successfully treated without penicillin. We used amoxicillin and probenecid for the first case-patient and amoxicillin, probenecid, and ceftriaxone for the second case-patient.

Melioidosis, an infectious disease with high mortality, caused by Burkholderia pseudomallei, is endemic in southeast Asia and northern Australia. In Indonesia, autochthonous cases have been rarely reported, with most cases being sporadic and occurring in travelers. Herein, we report a fatal case of neurological melioidosis in a traveler from Indonesia presenting with septic shock., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A 59-year-old male presented with fever, and was admitted for bacteremia due to gram-positive rod. All 5 sets of blood cultures obtained prior to the initiation of vancomycin tested positive for Bacillus subtilis. Based on the susceptibility test result, the antibiotics were changed to levofloxacin to complete a total of fourteen days treatment. The patient recovered without relapse over one year. Despite thorough examinations, the portal of entry of B. subtilis remained unclear. We retrospectively reviewed ten cases of bacteremia due to B. subtilis over 5 years in our hospital. The cases with positive B. subtilis blood cultures which were evaluated as contamination were excluded from the review. The most common portal of entry of B. subtilis was secondary bacteremia due to perforation or ileus (70%), followed by an unknown site (30%). B. subtilis should be considered not only as a contaminant but also as a true pathogen of bacteremia.

Relapsing polychondritis (RP) is a rare systemic disorder characterized by recurrent, widespread chondritis of the auricular, nasal, and tracheal cartilages. IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease characterized by the infiltration of IgG4-bearing plasma cells into systemic organs. Although 25% to 35% of patients with RP have a concurrent autoimmune disease, coexistence of RP and IgG4-RD is rare. We herein report a case of RP complicated by IgG4-RD. A 63-year-old man developed recurrent bilateral ear pain and swelling, recurrent blurred and decreased vision, and migratory multiple joint pain, sequentially within one year. Fourteen months after the first symptom, he experienced dry cough and dyspnea with exertion. A computed tomography (CT) scan detected interstitial pneumonia, swelling of bilateral submandibular glands, bilateral hilar and mediastinal lymphadenopathy, and several nodules in bilateral kidneys. His serum levels of IgG and IgG4 were elevated. The biopsy specimen of auricular cartilage showed infiltrations of inflammatory cells and fibrosis consistent with RP. The IgG4-positive cells were not observed in auricular cartilage. The patient met the diagnostic criteria of RP, including bilateral auricular chondritis, conjunctivitis, iritis and polyarthritis. The biopsy specimens of lung and kidney revealed the significant infiltrations of IgG4-positive plasma cells and fibrosis. We also diagnosed him as having IgG4-RD, affecting bilateral submandibular glands, hilar and mediastinal lymph nodes, lungs, and kidneys. Thus, RP preceded the onset of IgG4-RD. Corticosteroid therapy improved the symptoms and CT scan findings. In conclusion, RP and IgG4-RD do coexist; however, the pathogenesis of their coexistence is unknown.

Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution., ((c) 2010 Elsevier Inc. All rights reserved.)

MicroRNAs (miRNAs) are short (20-23 nt) RNAs that are sequence-specific mediators of transcriptional and post-transcriptional regulation of gene expression. Modern high-throughput technologies enable deep sequencing of such RNA species on an unprecedented scale. We find that the analysis of small RNA deep-sequencing libraries can be affected by cross-mapping, in which RNA sequences originating from one locus are inadvertently mapped to another. Similar to cross-hybridization on microarrays, cross-mapping is prevalent among miRNAs, as they tend to occur in families, are similar or derived from repeat or structural RNAs, or are post-transcriptionally modified. Here, we develop a strategy to correct for cross-mapping, and apply it to the analysis of RNA editing in mature miRNAs. In contrast to previous reports, our analysis suggests that RNA editing in mature miRNAs is rare in animals.

Unlabelled: Multi-mapping sequence tags are a significant impediment to short-read sequencing platforms. These tags are routinely omitted from further analysis, leading to experimental bias and reduced coverage. Here, we present MuMRescueLite, a low-resource requirement version of the MuMRescue software that has been used by several next generation sequencing projects to probabilistically reincorporate multi-mapping tags into mapped short read data., Availability and Implementation: MuMRescueLite is written in Python; executables and documentation are available from http://genome.gsc.riken.jp/osc/english/software/.

Background: MicroRNAs (miRNAs) are short single stranded noncoding RNAs that suppress gene expression through either translational repression or degradation of target mRNAs. The annealing between messenger RNAs and 5' seed region of miRNAs is believed to be essential for the specific suppression of target gene expression. One miRNA can have several hundred different targets in a cell. Rapidly accumulating evidence suggests that many miRNAs are involved in cell cycle regulation and consequentially play critical roles in carcinogenesis., Methodology/principal Findings: Introduction of synthetic miR-107 or miR-185 suppressed growth of the human non-small cell lung cancer cell lines. Flow cytometry analysis revealed these miRNAs induce a G1 cell cycle arrest in H1299 cells and the suppression of cell cycle progression is stronger than that by Let-7 miRNA. By the gene expression analyses with oligonucleotide microarrays, we find hundreds of genes are affected by transfection of these miRNAs. Using miRNA-target prediction analyses and the array data, we listed up a set of likely targets of miR-107 and miR-185 for G1 cell cycle arrest and validate a subset of them using real-time RT-PCR and immunoblotting for CDK6., Conclusions/significance: We identified new cell cycle regulating miRNAs, miR-107 and miR-185, localized in frequently altered chromosomal regions in human lung cancers. Especially for miR-107, a large number of down-regulated genes are annotated with the gene ontology term 'cell cycle'. Our results suggest that these miRNAs may contribute to regulate cell cycle in human malignant tumors.

Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.