Many viruses require the cleavage-activation of membrane fusion proteins by host proteases in the course of infection. This knowledge is based on historical studies of Sendai virus in the 1970s. From the 1970s to the 1990s, avian influenza virus and Newcastle disease virus were studied, showing a clear link between virulence and the cleavage-activation of viral membrane fusion proteins (hemagglutinin and fusion proteins) by host proteases. In these viruses, cleavage of viral membrane fusion proteins by furin is the basis for their high virulence. Subsequently, from the 2000s to the 2010s, the importance of TMPRSS2 in activating the membrane fusion proteins of various respiratory viruses, including seasonal influenza viruses, was demonstrated. In late 2019, severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) emerged and caused a pandemic. The virus continues to mutate, producing variants that have caused global pandemics. The spike protein of SARS-CoV-2 is characterized by two cleavage sites, each of which is cleaved by furin and TMPRSS2 to achieve membrane fusion. SARS-CoV-2 variants exhibit altered sensitivity to these proteases. Thus, studying the cleavage-activation of membrane fusion proteins by host proteases is critical for understanding the ongoing pandemic and developing countermeasures against it.

Klebsiella pneumoniae (Kp), which is associated with hospital-acquired infections, is extensively drug-resistant (XDR), making treatment difficult. Understanding the genetic epidemiology of XDR-Kp can help determine its potential to be hypervirulent (hv) through the presence of siderophores. We characterized the genomes of 18 colistin-resistant XDR-Kp isolated from 14 patients with complicated tract infection at an Indian healthcare facility. The 18 organisms comprised the following sequence types (STs): ST14 (n = 9), ST147 (n = 5), ST231 (n = 2), ST2096 (n = 1), and ST25 (n = 1). Many patients in each ward were infected with the same ST, suggesting a common source of infection. Some patients had recurrent infections with multiple STs circulating in the ward, providing evidence of hospital transmission. β-lactamase genes (bla_CTX-M-1, bla_SHV, and bla_ampH) were present in all isolates. bla_NDM-1 was present in 15 isolates, bla_OXA-1 in 16 isolates, bla_TEM-1D in 13 isolates, and bla_OXA-48 in 3 isolates. Disruption of mgrB by various insertion sequences was responsible for colistin resistance in 6 isolates. The most common K-type among isolates was K2 (n = 10). One XDR convergent hvKp ST2096 mutation (iuc+ybt+bla_OXA-1+bla_OXA-48) was associated with prolonged hospitalization. Convergent XDR-hvKp has outbreak potential, warranting effective antimicrobial stewardship and infection control.

Equine botulinum antitoxin is one of the most popular countermeasures for human botulism. The unitage of the antitoxin product is defined according to national minimum requirement or pharmacopoeia in each country by referring to national standard antitoxins for four types (A, B, E, and F). With the expected depletion of the national standard antitoxins, replacement national standard antitoxins are produced and standardized through collaboration of the National Control Laboratory and other participants, including manufacturer(s). Therefore, Japanese National Standard Botulinum Antitoxin Type A, Equine, was replaced according to the results of a collaborative study involving the National Institute of Infectious Diseases and KM Biologics Co., Ltd. The unitage of the replacement material was determined through mouse neutralization tests, which involved toxin-antitoxin mixture injection at pH 7.0. Potency value of 440 units/vial was obtained. However, the Japanese Minimum Requirement for Biological Products was revised, and the neutralization reactions were repeated at pH 6.0, for which considerably different potency value (656 units/vial) and survival profile of mice were obtained. In September 2021, the replacement material, Japanese National Standard Botulinum Antitoxin Type A, Equine, lot 2, was established with potency value of 656 Units/vial. The impact of pH-dependent change in potency on antitoxin quality control is discussed.

Latent tuberculosis infection (LTBI) with fibrotic lesions (FL) can progress to active tuberculosis (TB). Most previous studies have used tuberculin skin tests, which have lower specificity than interferon-gamma release assays (IGRAs), for LTBI diagnosis. This study evaluated the incidence of active TB among individuals with LTBI (diagnosed using IGRAs) and FL in Nishinari District, Osaka City. In total, 54 men (mean age: 68.7 years) were enrolled, of whom 10 (18.5%) were homeless, and 36 (66.7%) were welfare recipients. The median observation period was 1,084 days (range: 64–2,907 days). The incidence rate of active TB among individuals with LTBI and FL was 1.18 (95% confidence interval: 0.32–4.29) cases per 100 person-years. Among the 19 participants who had not been treated with anti-TB therapy, one (5.3%) progressed to active TB, and among the 30 participants who had completed anti-TB treatment, one (3.3%) progressed to active TB. The other 5 participants did not have TB. This study revealed the incidence of active TB among individuals with LTBI, diagnosed using IGRAs, and FL in a vulnerable urban population. The higher incidence than that reported in previous studies reinforces the importance of improved LTBI management strategies, including chest radiography screening, and LTBI treatment.

We evaluated the cell invasion ability (CIA) of non-invasive Streptococcus dysgalactiae subsp. equisimilis using human keratinocytes and determined the association of CIA populations with their hosts and microbiological traits. Forty-two isolates from humans and companion animals were selected with host information. In addition to CIA, virulence-associated gene (VAG, spegg–ska–scpA–inlA–sicG–brpA–prtF1–prtF2–lmb–cbp–srtp1–srtp2) profiling, emm genotyping, multilocus sequence typing, and antimicrobial resistance (AMR) phenotyping/genotyping were performed. We designated CIA values higher than the mean of all isolates as high-frequency and those lower than the mean as low-frequency. Differences in the CIA between the different sources and Lancefield groups were assessed. We analyzed the association between high- and low-frequency CIA and VAG, emm genotype, sequence type/clonal complex, and AMR phenotype/genotype. Based on the mean (19.368 colony-forming units/100 cells) of 42 isolates, eight isolates had high-frequency CIA, whereas 34 had low-frequency CIA. We found an association between low-frequency CIA population and group G isolates, as well as a link between high-frequency CIA population and group C isolates. We also observed associations between low-frequency CIA population and oral/respiratory tract origin, ska, scpA, and lmb detection, and the AMR phenotype. Our observations suggest potential associations between high-/low-frequency CIA and the group, source, VAG, and AMR phenotypes.

General vaccine hesitancy is a global concern. Clarifying general vaccination readiness and the psychological factors comprising it is important. Previous studies reported that Japan has one of the lowest vaccine confidence levels worldwide. However, the status of other psychological factors comprising general vaccination readiness in Japan remains unclear. Therefore, we aimed to clarify the status of seven psychological factors comprising general vaccination readiness and their patterns in Japan. This descriptive study utilized data from a large-scale nationwide internet survey (Japan Society and New Tobacco Internet Survey 2023 study, N = 31,037). Seven psychological factors were assessed using the 7C of vaccination readiness scale. Cluster analysis was performed using k-means++ clustering to clarify patterns. Of the seven factors, support for social monitoring of people refusing vaccination (e.g., vaccine passports) was very low among the participants. Cluster analysis showed that the participants’ vaccination readiness could be classified into six patterns, of which the very low vaccination readiness cluster, with the lowest scores for most psychological factors, accounted for 11.1% and was more common among those aged 30–49 years (13.1–16.4%). Individuals in this cluster may refuse to receive recommended vaccines.

CoronaVac is one of the most widely administered COVID-19 vaccines in Indonesia. Previous studies have documented its effectiveness in protecting against COVID-19 in several countries. This study aimed to assess the long-term immunogenicity of CoronaVac in individuals with comorbidities or a history of SARS-CoV-2 infection. The total anti-N Ig and anti-S-RBD Ig levels at 7 and 26 weeks after the second dose of vaccine were documented in 194 health workers. The participants were divided into groups based on their comorbidities and history of SARS-CoV-2 infection. The antibody titers did not differ according to comorbidity status or history of SARS-CoV-2 infection. The total anti-nucleocapsid Ig and total anti-S-RBD Ig levels were significantly lower in individuals without a history of SARS-CoV-2 infection. These results indicate that CoronaVac induces a lower specific antibody response than natural infection and less long-term immunogenicity.

Salmonella enterica subsp. enterica serovar Typhimurium has recently emerged worldwide as a producer of extended-spectrum β-lactamase (ESBL). However, drug-resistant clinical isolates are rare in Japan. The common types of ESBLs found are the CTX-M-type β-lactamases, including novel β-lactamases such as CTX-M-64. CTX-M-64 has a chimeric structure comprising a combination of the CTX-M-1 and CTX-M-9 groups. In 2017, S. Typhimurium was isolated from stool, blood, and urine cultures of an 82-year-old man. Herein, we describe the discovery of a clinical isolate of S. Typhimurium in Japan. Antimicrobial susceptibility testing revealed that the isolate was resistant to third- and fourth-generation cephalosporins, including ceftazidime and monobactam. The minimum inhibitory concentrations of ceftazidime and ceftriaxone were restored by administration of clavulanic acid. Whole-genome sequencing analysis revealed that the isolate harbored the bla_CTX-M-64 gene on an IncHI2/IncHI2A-type plasmid, with an assembly length of 174,477 bp. The genetic structure of the region surrounding the bla_CTX-M-64 gene, ISKpn26-ΔISEcp1-bla_CTX-M-64-orf477, was shared only with the chromosome sequence of S. Typhimurium detected in food-producing chickens in Guangdong, China. Although rare, S. Typhimurium can induce bloodstream infections and produce ESBL. To our knowledge, this is the first report of a CTX-M-64-producing Enterobacterales clinical isolate of domestic origin in Japan.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is prevalent worldwide, and effective and safe vaccines against this virus have been developed. Although trends in antibody titers after vaccination and/or SARS-CoV-2 infection have been reported, long-term studies with high frequency of measurements are limited. This report describes the long-term and detailed trends in the antibodies against SARS-CoV-2 S protein receptor-binding domain (S-RBD) measured repeatedly after vaccination and/or infection in 3 healthcare workers. All healthcare workers were administered 30 µg of the messenger RNA vaccine, BNT162b2, during all vaccinations. The peak value of the SARS-CoV-2 S-RBD titer was reached at 1–2 weeks after vaccination and then decreased by half within 8 weeks after vaccination; the peak values of the antibody titer increased with repeated vaccinations. In contrast, after SARS-CoV-2 infection, the peak value of the antibody titer was reached at 4–8 weeks after infection, and the antibody titer remained elevated up to 16–40 weeks after the peak. This report describes the long-term and detailed trends in the anti-SARS-CoV-2 S-RBD titers, showing different patterns after vaccination and/or SARS-CoV-2 infection.

To demonstrate the transmission cycle of Shimokoshi-type Orientia tsutsugamushi in Shimane Prefecture, field rodents were captured from areas where four human infections caused by the pathogen have been reported. The rodents were investigated for the transmission cycle of the pathogen based on the pathogen’s genome, antibodies against the pathogen, and the vector of the pathogen (Leptotrombidium palpale). In addition, the vector was captured from the soil in the study area. A total of 44 rodents were captured. No O. tsutsugamushi DNA was detected in the blood or spleen samples by real-time polymerase chain reaction. However, a specific antibody against the pathogen was detected in 2 out of 44 (4.5%) rodents using the indirect immunoperoxidase method, indicating the presence of the pathogen in the study area. Although 29 L. palpale were identified, DNA detection was not performed because of the insufficient number of vectors, based on the DNA detection rate in previous studies. However, the identification of the vector, as well as the specific antibody in rodents, suggests the presence of the transmission cycle of Shimokoshi-type O. tsutsugamushi in Shimane Prefecture.