Gastrointestinal manifestation is the most common complication in HIV-infected patient especially enteropathy. Faecal calprotectin is applicable to gut inflammatory biomarker in general population while the sensitivity in HIV-infected patient is remained unknown. This cross-sectional study evaluated between HIV-infected children and control group with the age of 2-18 years old in Dr. Soetomo General Hospital, Surabaya, Indonesia, 19 and 27 samples respectively. This study conducted with collecting stool sample from previous randomized controlled trial using Epitope Cat. No. 30356. The data analysed using Mann-Whitney as non-parametric test and significant with p-value < 0.05. Most of the HIV infected patients are on 1^st therapy regimen (78.9%) and all of them are on therapy more than 1 year duration. The mean and standard deviation of the concentration of CD4, percentage of CD4, and ratio of CD4/CD8 were 1,042.47 ± 450.38, 26.01 ± 9.24, and 0.71 ± 0.43, respectively. The median faecal calprotectin level in the HIV-infected group was 63.50 ng/ml (IQR: 21.50 – 203.50), compared to 17.00 ng/ml (IQR: 13.00 – 33.00) (p = 0.004). Faecal calprotectin is significantly higher in HIV-infected patients compared to the control group. Hence, faecal calprotectin can be used as a gut inflammatory biomarker especially in HIV-infected patients.

Patients with mental illnesses are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and are more likely to develop severe disease when infected. Therefore, in many countries, they have been considered a priority group for vaccination. However, the immunological effects of vaccination in these patients remain insufficiently studied. In this study, we investigated changes in serum neutralizing antibody titers against SARS-CoV-2 over a two-year period. Fifty-three participants who had experienced a coronavirus infection (COVID-19) outbreak in a closed psychiatric ward in September 2020 were followed. Antibody titers were measured after natural infection and subsequent vaccination. Neutralizing antibody titers declined over time, and 20% of patients fell below the positivity threshold within six months after infection. In contrast, all patients who received two subsequent mRNA vaccinations maintained high antibody titers for at least six months after vaccination. These findings suggest that vaccination provides effective and sustained humoral immunity in psychiatric patients with a history of COVID-19 infection.

Different types of Botulinum neurotoxins (BoNTs) cause human botulism. Among them, type F botulism, caused by genetically diverse BoNT/F subtypes, is rare and may be overlooked despite its clinical importance. Toxin-neutralizing human antibodies, which carry the minimum risks of inducing serum sickness or anaphylaxis, are ideal for the treatment of human botulism. In this study, we generated human monoclonal antibodies (mAb) against BoNT/F using trans-chromosomic monoclonal antibody (TC-mAb) mice. A recombinant toxin fragment consisting of the light chain and the heavy chain N-terminal domain (L-H_N) of BoNT/F subtype 1 was selected as the antigen because this subtype is used as the reference antigen for currently available antitoxin preparations. Three mAbs (126, 134, and 146) were obtained and reconstructed in a human IgG format. Although the mAbs did not significantly inhibit VAMP2 cleavage in primary cultured neurons, they exhibited partial neutralizing activities in mouse bioassays. In addition, we found that the combinatorial use of 126 and 146 enhanced neutralizing activity. These findings provide important information for the future development of human therapeutic mAbs against BoNT/F.

Dengue is a re-emerging tropical disease transmitted by mosquitoes. This cross-sectional study was conducted in the Department of Paediatrics of a tertiary care centre in South India over two years. Children and adolescents aged 0-15 years who presented with fever and were confirmed to have dengue by serological tests were included in this study. Blood was collected and sent for complete blood count (CBC) on day 3 of illness. Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were derived. The sensitivity of NLR and PLR was 68.4% and 96.8% respectively, while the specificity of NLR and PLR were 41.7% and 66.7% respectively. Although PLR was found to have higher sensitivity and specificity, NLR was found to have an increased positive predictive value. The platelet-lymphocyte ratio demonstrates superiority by overall accuracy, specificity, and sensitivity, proving to be a more effective marker for identifying severe dengue cases. NLR and PLR demonstrated a strong positive correlation (r = 0.83, p <0.001). The clinical utility of these ratios has been extensively studied in other diseases, such as sepsis and COVID-19, especially in adults, but has been underutilized in children due to the lack of knowledge and limited research.

Dengue remains a major public health concern in Indonesia. This study aimed to describe the epidemiology, clinical characteristics, immune responses, and genotype characterization of dengue virus (DENV) infections in Tangerang Regency, Indonesia. A year-round prospective surveillance was conducted from January 2024-January 2025 at a district hospital and two primary health centers. Febrile patients aged ≥4 years were tested using dengue NS1, IgM/IgG rapid tests, ELISA, and RT-PCR, and serum biomarkers (angiopoietin-2, IL-6, ferritin, sCD163) were quantified. Of 404 participants, 240 (59.4%) had confirmed dengue. Among RT-PCR–serotyped cases (n=192), the distribution was DENV-2 63/192 (32.8%), DENV-1 60/192 (31.3%), DENV-3 47/192 (24.5%), and DENV-4 22/192 (11.5%). Among hospitalized dengue cases (n=144), secondary infection (131/144, 91.0%) was associated with severe disease (adjusted OR=10.25; 95% CI: 1.71–197.90, p=0.034). Biomarker levels were elevated in dengue cases but did not discriminate severity, indicating the need for validation in larger cohorts using standardized definitions. Sequencing identified DENV-1 genotypes I and IV, DENV-2 Cosmopolitan, DENV-3 genotype I, and DENV-4 genotype IIa; one DENV-4 isolate carried an EDIII E384 D→H substitution warranting further investigation. Continued genomic surveillance and vaccine development that induces balanced, serotype-specific immunity are needed to support national and global dengue control.

The rise of extended-spectrum β-lactamase (ESBL) and carbapenem-resistant Enterobacterales (CRE) has severely limited treatment options in India. Cefepime–enmetazobactam (FPE), a novel β-lactam/β-lactamase inhibitor combination approved by the US FDA in 2024, shows promise as a carbapenem-sparing agent. A total of 383 non-duplicate resistant isolates of Escherichia coli and Klebsiella pneumoniae subsp. pneumoniae. were studied (January 2023–December 2024) at a tertiary-care centre in New Delhi. Isolates were categorized as third generation cephalosporin resistant but carbapenem-susceptible (Group A, n=258) or carbapenem-resistant (Group B, n=125). Antimicrobial susceptibility was determined by CLSI disc diffusion, and synergy with aztreonam was evaluated. Among Group A isolates, FPE exhibited the highest activity—95.4% E. coli and 97.4% K. pneumoniae susceptibility—outperforming ceftazidime-avibactam (88.1% and 84.6%) and Piperacillin tazobactam (5.4% and 10.2%, respectively). In Group B (CRE), activity was significantly lower: FPE (13% E. coli, 14.3% K. pneumoniae), CZA (31.9% and 7.1%), and PT (0%). ESBL production was observed in 88% of Group A isolates, predominantly bla_CTX-M (94%), while all CRE carried bla_NDM and bla_OXA-48 genes. FPE–aztreonam synergy was infrequent (≤4%). Cefepime–enmetazobactam demonstrated superior in vitro activity to CZA and Piperacillin Tazobactam against ESBL-producing but carbapenem-susceptible Enterobacterales, making it a potent carbapenem-sparing option.

Human parechovirus type 5 (HPeV-5) is rarely reported, and, thus, its clinical and virological features remain unclear. This study describes the first cluster of HPeV-5 meningitis in Japan and characterizes its clinical, laboratory, and molecular features. Six infants aged 13-42 days were identified at three municipal hospitals in Kobe, Japan, during a six-week period in summer 2025. Symptoms included fever (6/6), mottled skin (4/6), poor feeding (3/6), and rash (2/6). None developed thrombocytopenia, liver dysfunction, or cerebrospinal fluid (CSF) pleocytosis; one had leukopenia. Two infants who were tested had hyperferritinemia that persisted after defervescence. Fever resolved within three days in all infants, and all were discharged without sequelae. A polymerase chain reaction detected HPeV-5 in the CSF of all infants. A phylogenetic analysis demonstrated high VP1 nucleotide identity (>97%) with strains in Sapporo, Japan (2018), Australia (2019), and USA (2024), suggesting the circulation of a nearly identical lineage across multiple regions. HPeV-5 was also detected in 14 additional non-meningitis cases during the same period, indicating concurrent circulation in the community. These results indicate that HPeV-5 causes meningitis in young infants, even without CSF pleocytosis, and was associated with favorable outcomes in this case series. Continued molecular epidemiological surveillance is warranted.

Human parainfluenza virus type 3 (HPIV-3), an increasingly significant respiratory pathogen affecting both pediatric and elderly populations, currently lacks effective prophylactic or therapeutic interventions. The development of antibody-based therapeutics with the potential to prevent or treat HPIV-3 infection remains an active area of investigation. However, a major limitation of such antibody therapies is the emergence of escape mutant strains. Combination therapy employing multiple neutralizing antibodies targeting distinct epitopes has been explored as a strategy to circumvent viral escape in influenza and human immunodeficiency virus infections. However, the probability of obtaining multiple neutralizing antibodies, including those against HPIV-3, is generally low. Here, to maximize the presentation of viral surface epitopes to immune cells, we purified HPIV-3 virus using magnetic bead–based technology. The resulting antigen–magnetic bead complexes were immobilized and used to immunize mice. This strategy employs viable and infectious virion as immunogens, thereby enabling immune cells to recognize the native antigenic architecture of the viral surface with high fidelity. This method, which permits immunization while preserving the viral surface structure to the greatest extent and may be broadly applicable to many viruses, provide a simple and rapid approach for developing therapeutic antibodies during public health emergencies.

Hepatitis B virus (HBV) remains a major global public health concern, with numerous nosocomial and occupational outbreaks reported. Preventing indirect HBV transmission through effective disinfection is crucial. This study evaluated the virucidal activity of chlorine dioxide (ClO₂) against HBV and compared it with sodium hypochlorite (NaClO). Pretreatment of HBV with ClO₂ at 10, 100, and 250 ppm (mg/L) for 1 min reduced hepatitis B surface antigen (HBsAg) release to 65.5%, 21.9%, and 7.0%; hepatitis B core (HBc)-positive cells to 59.1%, 27.0%, and 6.6%; intracellular HBV RNA to 71.5%, 31.6%, and 3.0%; and extracellular HBV DNA to 82.2%, 42.6%, and 14.1%, respectively. At identical concentrations, NaClO produced smaller reductions. In the presence of organic matter, no significant reduction in ClO₂ activity against HBV was observed. ClO₂ demonstrated approximately 2.2-fold greater anti-HBV potency than NaClO with and without bovine serum albumin and sheep erythrocytes. Neutralizer, cell-permissiveness, and ultrafiltration controls supported direct viral inactivation. These findings indicate that ClO₂ showed stronger in vitro anti-HBV activity than NaClO within the tested concentration range and conditions.

In recent years, the number of Group A Streptococcus-associated infections has increased significantly in Akita Prefecture. An analysis of isolates collected between 2017 and 2025 revealed that the intermediate M1_13SNPs lineage has gained predominance as the cause, surpassing both the ancestral M1_global and globally prevalent hypervirulent M1_UK lineages. M1_13SNPs specifically harbored speC, spd1, and sdaD2; the latter was also present in most of M1_UK. Furthermore, M1_13SNPs possessed unique mutations in sic, with the majority of the identified sic genotypes being novel variants. In the southern region of Akita, where the outbreak was particularly intense, region-specific subvariants characterized by aspartic acid substitutions were identified. These findings suggest that the surge in Group A Streptococcus-associated infections in Akita Prefecture was not merely caused by the introduction of a widespread global clone but was driven in part by the dissemination of the M1_13SNPs lineage, which possesses distinctive genetic features and may have undergone localized evolutionary adaptation.

Legionella poses significant health risks in recreational waters and causes legionellosis. Although sodium hypochlorite (NaClO) is widely used for water disinfection, it has several disadvantages such as skin irritation, corrosion of surfaces and formation of harmful disinfection by-products. Hypochlorous acid (HClO) has emerged as an alternative disinfectant that may overcome these limitations. Here, we showed that 5.0 ppm highly purified HClO (iPOSH) reduced approximately 7.7 log CFU/mL of L. pneumophila to below the detection limit (10 CFU/mL) within 60 sec whereas 5.0 ppm NaClO required 180 sec to achieve the same level of reduction. Notably, iPOSH retained greater antibacterial activity than NaClO even in the presence of organic matters. iPOSH also exhibited comparable antibacterial efficacy across a pH range of 6.0–8.0. In Onsen water, 0.4 ppm iPOSH reduced approximately 7.7 log CFU/mL of L. pneumophila to below the detection limit within 60 min whereas 0.4 ppm NaClO achieved only less than 1 log CFU reduction after 60 min. These results demonstrate that 0.4 ppm iPOSH, the minimum chlorine concentration permitted for disinfection of public bathing facilities by the Japanese Ministry of Health, Labor and Welfare, exhibits effective antibacterial activity against L. pneumophila, and hence a promising alternative to NaClO.

A phase III open-label study evaluated the immunogenicity and safety of the 9-valent human papillomavirus (9vHPV) vaccine in Japanese boys and girls. Japanese boys aged 9-15 years (n = 105) received a 3-dose (Day 1, Month 2, and Month 6) regimen; Japanese boys (n = 104) and girls aged 9-14 years (n = 105) received a 2-dose (Day 1 and Month 6) regimen. Antibody responses to HPV6/11/16/18/31/33/45/52/58 were assessed at Month 7, 18, and 30 using a competitive Luminex immunoassay. Injection-site adverse events (AEs; Days 1 to 5 post-dose), systemic AEs (Days 1 to 15 post-dose), and serious AEs (duration of study) were assessed. At Month 7, for HPV types targeted by the 9vHPV vaccine, seroconversion rates were 100% in all three arms, and in cross-study comparisons with efficacy studies, anti-HPV geometric mean titers in boys were noninferior to those in Japanese men aged 16-26 years, and in girls were noninferior to those in Japanese women aged 16-26 years. Most injection-site AEs were mild to moderate in intensity. No deaths or vaccine-related serious AEs were observed. These results support immunobridging of efficacy findings in Japanese men and women to Japanese boys and girls. The 9vHPV vaccine was generally well tolerated.

The recent geographical expansion of Oropouche virus (OROV) highlights the critical need to evaluate vector competence in non-endemic regions. This study aimed to evaluate the susceptibility of major Japanese mosquito populations (Culex quinquefasciatus, Cx. pipiens pallens, and Aedes albopictus) and a South African reference strain of Cx. quinquefasciatus to the OROV prototype strain (TRVL9760) by intrathoracic injection (ITI) and oral exposure (OE) experiments. Following ITI, 100% of the tested mosquitoes developed infections with high viral replication, particularly Ae. albopictus, demonstrating its robust cellular permissiveness. Conversely, OE yielded low infection rates in the thorax and abdomen (0–18.9%) and failed to cause systemic dissemination to secondary tissues (head, wings, and legs). These results demonstrate that the stringent midgut barriers that prevent OROV dissemination are maintained in both Japanese and reference mosquito strains. However, the robust viral replication observed upon bypassing these barriers reveals a significant latent susceptibility. By elucidating these dynamics, this study provides the first scientific evidence of the intrinsic susceptibility of Japanese mosquitoes to OROV. This foundational knowledge is not only critical for assessing current transmission risks but also serves as an essential baseline to determine whether contemporary epidemic lineages might overcome these physiological constraints in the future.

Campylobacter jejuni and C. coli are major causes of foodborne illness worldwide. Increasing antimicrobial resistance (AMR) and the implication of C. jejuni in Guillain–Barré syndrome (GBS), a post-infectious complication, are serious public health concerns. In this study, we characterized Campylobacter isolates from foodborne illness cases in Saitama Prefecture, Japan, focusing on AMR profiles, CPS (Penner) genotypes, multilocus sequence types (STs), and GBS-associated LOS biosynthesis genes. High resistance rates to quinolones and tetracycline were observed in C. jejuni (46.6%, 26.4%) and C. coli (50.0%, 60.0%), and C. coli also showed erythromycin resistance (25.0%), whereas C. jejuni remained susceptible. CPS genotyping of 148 C. jejuni isolates showed a high typeability rate (97.3%), supporting its utility for molecular surveillance. In a 40-isolate C. jejuni subset, MLST revealed that clonal complex 21 (CC21) predominated and ST-4526 was the most common ST. All ST-4526 isolates were quinolone-resistant and carried the GBS-associated genes cst-II (Thr51 variant), cgtA, and cgtB. The ST distribution of C. jejuni overlapped with that of chicken-derived strains, suggesting poultry as a major source of infection. These findings highlight the utility of CPS genotyping and the public health importance of the quinolone-resistant ST-4526 lineage carrying GBS-associated LOS biosynthesis genes.

Long COVID remains a substantial public health challenge, and the relationship between post-COVID-19 vaccination and symptom persistence remains uncertain. This prospective longitudinal study evaluated long COVID symptom trajectories according to post-COVID-19 vaccination status. Adult patients who were unvaccinated at the time of COVID-19 diagnosis were followed at 1, 3, 6, and 9 months and categorized according to vaccination status. Symptom Tool (ST) and Impact Tool (IT) scores and SARS-CoV-2 IgG antibody levels were assessed longitudinally. A total of 59 patients (mean age 43.1±14.1 years; 45.8% male) were included, of whom eight were vaccinated. The most frequently reported symptoms were memory problems, fatigue, brain fog, word-finding difficulties, and excessive sweating. Baseline characteristics were broadly comparable between groups. ST and IT scores decreased significantly over time in the overall cohort; however, no statistically significant association between vaccination status and symptom trajectories was identified. SARS-CoV-2 IgG antibody levels were higher among vaccinated participants but were not associated with symptom burden. Given the small sample size and substantial group imbalance, the study is underpowered and the findings should be interpreted cautiously. Larger prospective studies are needed to better clarify the relationship between post-COVID-19 vaccination and long COVID outcomes.

Outpatient antibiotic use for acute upper respiratory tract infections contributes to antimicrobial resistance, yet data from Japanese tertiary outpatient settings are limited. We retrospectively reviewed outpatient encounters at National Hospital Organization Osaka National Hospital (Osaka, Japan) from April 2020 to March 2024 with ICD-10 diagnoses J00, J01, J02, or J06. Oral antibiotic prescriptions were mapped to the 2022 World Health Organization Access/Watch/Reserve classification and assessed using a conservative, guideline-derived operational framework across indication, agent, and intended duration; multivariable logistic regression evaluated factors associated with algorithm-defined guideline nonconcordance. Among 2,431 encounters, antibiotics were prescribed in 19.5% (475/2,431). Watch-group agents accounted for 64.0% (304/475). Under the operational criteria, 92.2% (438/475) of prescriptions were algorithm-defined guideline-nonconcordant, most often because antibiotics were not indicated for the recorded diagnosis. Nonconcordant prescribing was strongly associated with age ≤12 years (adjusted odds ratio [aOR] 7.56) and acute pharyngitis (aOR 2.56 vs acute rhinosinusitis). Because assessment relied on ICD-10 and prescription data, these estimates should be interpreted as algorithm-defined guideline nonconcordance rather than definitive clinical inappropriateness. Findings highlight priorities for outpatient antimicrobial stewardship and support prospective validation with chart-level clinical data and microbiological testing.

Foodborne outbreaks caused by the Bacillus cereus group remain a public health concern, yet genome-based outbreak investigations in Japan remain limited. Whole-genome sequencing (WGS) and core-genome single-nucleotide polymorphism (cgSNP) analyses were used to characterize two foodborne outbreaks that occurred in Okinawa Prefecture, Japan, in 2021 (OB1) and 2022 (OB2). From the two outbreaks, 30 cereulide synthetase gene-positive isolates from patients, implicated foods (OB1 only), and food preparation environments were analyzed. All isolates were classified as B. paranthracis and were assigned to sequence type 26 (ST26) and panC group III. Although the two outbreaks involved B. paranthracis ST26 isolates and appeared similar by conventional typing, cgSNP analysis revealed low within-outbreak diversity (0–2 SNPs in OB1; 0–3 SNPs in OB2), while clearly separating the two outbreaks (353–356 SNPs), indicating that genetically distinct strains caused two outbreaks occurring one year apart in the same prefecture. In OB1, cgSNP clustering supported source attribution by linking the isolates from patients, foods, and the environment to the implicated catering facility. Overall, WGS-based SNP analysis enabled high-resolution discrimination and strengthened the epidemiological interpretation of the B. cereus group outbreak investigations.

Food poisoning caused by human norovirus genotype GII.17 affecting 73 individuals occurred in a single commercial building in Sapporo, Hokkaido, Japan, from late December 2024 to early January 2025. An epidemiological and environmental investigation was carried out and it was identified that the potable water contaminated with the virus was the sole factor for patients with gastrointestinal symptoms. Furthermore, it was revealed that the building’s water distribution system was tainted with the virus because the potable water storage tank for supply in the building's underground system was contaminated by sewage which flowed from the wastewater tank. A malfunction of the tank drainage system caused an overflow of sewage containing norovirus into the potable water storage tank, contaminating the building’s water supply. Although the mechanism causing this norovirus outbreak is infrequent, ageing building water infrastructure may increase such risks in future, unless appropriate maintenance is regularly performed.

Rubella is an acute, contagious viral illness that is generally mild, yet infection during early pregnancy can cause congenital rubella syndrome (CRS), a serious condition associated with deafness, blindness, congenital heart defects, and developmental disabilities. Although vaccination is the only effective preventive measure, rubella continues to circulate in regions with low immunization coverage. This study assessed the pre-vaccination seroprevalence of rubella IgM antibodies among women of reproductive age in Southeast Nigeria. A retrospective cross-sectional study was conducted from 2020 to 2024 among 405 women aged 15–49 years across five states in Southeast Nigeria. Serum samples were tested for rubella IgM antibodies using ELISA. Rubella IgM seroprevalence was 6.7% (27/405). Adolescents, 15–19 years had the highest positivity (11.7%), with prevalence declining steadily with age to 1.9% among women aged 30–34 years. Rubella positivity peaked in 2020 (16.0%) and 2024 (14.5%), with Imo State showing the highest prevalence (10.1%) and an incidence of 7.3 per 1,000,000 population. Rubella IgM positivity among women of childbearing age indicates ongoing transmission and susceptibility, particularly among adolescents. These findings provide baseline data for assessing vaccine impact and highlight the need for stronger surveillance and improved uptake to prevent CRS in Nigeria.

The economic burden of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) and caregiver quality of life (QOL) were assessed in a population-based epidemiological study of infant RSV LRTI in Chiba, Japan. Medical costs were calculated based on diagnosis procedure data, and multiplied by the average number of hospitalization days. Outpatient medical costs were calculated as the cost per visit and laboratory fees. Productivity loss was calculated by multiplying the number of days spent in the care of guardians. The QOL of caregivers was assessed by directly administering the EuroQol five-dimensional-five-level (EQ-5D-5L) questionnaire to guardians. These data can be extrapolated to the national level, estimating an overall economic burden of JPY 5.3 billion, including JPY 2.5 billion in medical expenses and JPY 2.8 billion in productivity loss. Low QOL scores were observed, with 70–80% of respondents experiencing issues in the “anxiety and depression” and “usual activity” including mobility and self-care dimensions of the EQ-5D-5L scale. Stratified analysis revealed lower QOL scores among those with RSV infection. RSV LRTI imposes a significant social and economic burden on children and their caregivers. This information could be instrumental in advancing discussions on RSV preventive measures in the National Immunization Program.

We developed a highly sensitive and reproducible enzyme-linked immunosorbent assay (ELISA) and a qualitative immunochromatography (IC) test to specifically measure antibodies against tetanus toxoid. These methods detect tetanus antibodies in human, mouse, rabbit, and horse sera. These assays demonstrated high accuracy and precision for mouse and human samples. Using the developed ELISA, we quantified tetanus antibody titers in a mouse immunization model (tetanus toxoid potency test) and in human samples. The relative potency of tetanus toxoid calculated from ELISA titers was comparable to that determined by the traditional in vivo toxin challenge method. In human pooled plasma, ELISA titers correlated strongly with neutralizing antibody titers (r = 0.9826), enabling the estimation of the latter. Furthermore, ELISA titers correlated highly with results from the Kaketsuken particle agglutination method (r = 0.9866) and the novel IC (r = 0.8209). These findings demonstrate the utility of these methods for evaluating vaccine efficacy and immune responses, suggesting broad applications in basic research and clinical settings.

Rubella elimination in Japan was verified in September 2025; however, importation and immunity gaps can still precipitate outbreaks. We investigated a multi-prefecture rubella outbreak in 2016 linked to an introductory training course for foreign workers. After a rubella case was reported in Saitama Prefecture on June 6, 2016, we investigated the training facility and conducted active nationwide surveillance. We collected roster and dispatch information, monitored cases reported to the National Epidemiological Surveillance of Infectious Diseases, and interviewed trainees, host-company staff. Ninety-two trainees were dispatched to 41 companies in 23 prefectures. Thirteen rubella cases were identified. Ten patients were Vietnamese trainees, nine were likely infected during group training, and one was suspected to have imported rubella from Vietnam. Three individuals were likely infected at host companies, including two Japanese supervisors. No patient had documented records of a rubella-containing vaccine. Viruses from three cases belonged to genotype 2B. A single importation into a congregate training setting can rapidly create multi-prefecture exposure. Vaccination and/or verification of immune status among incoming trainees and susceptible host-company workers is essential to prevent similar events and sustain rubella elimination in Japan.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to heterogeneous clinical outcomes, suggesting that dysregulated host immune responses and inflammation contribute to divergent disease trajectories. We examined early immune correlates of disease severity using 32-week-old C57BL/6J mice and evaluated whether modulation of regulatory T cells (Tregs) would alter disease outcome. Oral administration of the CDK8/19 inhibitor AS2863619 did not markedly improve early weight loss, gross lung inflammatory scores, bronchoalveolar lavage fluid (BALF) viral RNA levels, or histopathological findings. Despite this limited impact on clinical outcomes, AS2863619 increased the frequency of KLRG1⁺ subsets in lung Foxp3⁺ CD4⁺ Tregs at 5 days post-infection. Across infected animals, lung Foxp3⁺ CD4⁺ Treg numbers inversely correlated with early weight loss. In parallel, several BALF inflammatory cytokines and chemokines were associated with disease severity, and the frequency of KLRG1⁺ Tregs inversely correlated with multiple inflammatory mediators. These findings indicate that endogenous lung Treg numbers and KLRG1⁺ Treg frequencies were linked to a less inflammatory airway milieu during acute SARS-CoV-2 infection.

Klebsiella quasipneumoniae is a member of the Klebsiella pneumoniae complex that is difficult to distinguish from K. pneumoniae using conventional laboratory methods, and information on its clinical manifestations is limited. We describe the first known case of invasive infection with hypervirulent K. quasipneumoniae subsp. similipneumoniae in Japan. A 65-year-old woman with pancreatogenic diabetes mellitus presented with fever and nausea. Computed tomography revealed a liver abscess and multiple pulmonary nodules with cavitation suggestive of septic pulmonary emboli. Blood cultures yielded an isolate identified as K. pneumoniae complex. Whole-genome sequencing (WGS) subsequently identified the isolate as K. quasipneumoniae subsp. similipneumoniae, sequence type 367 (ST367) and capsular type K1 (KL1). The isolate exhibited a hypermucoviscous phenotype and harbored the virulence-associated genes iroBCDN, iucABCD/iutA, rmpA/A2, and peg-344. The patient improved following antimicrobial therapy with meropenem for 10 days, followed by cefmetazole for 13 days, and was discharged home after a hospital stay of 81 days. This case highlights the potential for invasive infection caused by hypervirulent K. quasipneumoniae, the usefulness of WGS for species identification, and the need for ongoing clinical and genomic surveillance to monitor the emergence of this pathogen.

Dengue remains a global health concern, especially in tropical regions like Indonesia. As of July 2024, there were 149,866 reported cases and 844 deaths, with children aged 0–14 years accounting for 63% of fatalities. Dengue presents a wide clinical spectrum, ranging from asymptomatic infection to Severe Dengue. Early detection of Severe Dengue still heavily relies on clinical warning signs, which are often unreliable. This study aimed to identify potential biomarkers to predict Dengue severity in children. An observational study using secondary data from medical records at RSSA Malang (2014–2022) was conducted, involving 304 pediatric patients (161 Severe Dengue, 143 Non-Severe Dengue). Patient characteristics such as gender, age, weight, nutritional status, and hospital stay duration showed no significant correlation with severity. However, significant differences were found in several biomarkers, notably SGOT, SGPT, ΔHb, PT, albumin, platelets, monocytes, and NLR. SGPT (AUC 0.894; OR 24.3) and SGOT (AUC 0.884; OR 16.148) emerged as the most predictive biomarkers. SGPT showed the highest diagnostic performance with 73% sensitivity, 90% specificity, and a cut-off value ≥52 µ/dL, indicating a 24.3-fold increased risk for Severe Dengue. SGPT may serve as a reliable early indicator of severity in pediatric Dengue cases.

Cellulitis is one of the most common forms of skin and soft tissue infections, traditionally attributed to beta-hemolytic streptococci and Staphylococcus aureus. While Gram-negative organisms, particularly nonfermentative gram-negative bacilli (NFGNB), are ubiquitous in soil and aquatic ecosystems, they are rarely reported as causative pathogens of cellulitis. We report a case of metachronous cellulitis caused by two species of NFGNB: Sphingobacterium and Myroides species. An 81-year-old male was admitted with cellulitis of the left upper extremity. Sphingobacterium species was identified from blood cultures using Oxford Nanopore Technologies MinION sequencer. The patient was treated with antibiotics and recovered. Eleven months later, the patient was readmitted with similar symptoms of cellulitis in the left upper extremity. Myroides species was identified from blood cultures using MinION sequencer and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass-Spectrometry. The occurrence of cellulitis caused by NFGNB is rare, and this case is unique because two different NFGNB species caused cellulitis at separate time points.

Tick-borne encephalitis (TBE) is a severe neurological disease caused by infection with the TBE virus (TBEV), primarily transmitted to humans through tick bites. As there is no effective treatment, prevention through vaccination and avoidance of tick bites is essential. In Japan, only five cases had been reported up to 2023, all from Hokkaido, the northernmost main island. Here, we report the sixth case of TBE in Japan. The patient was a 58-year-old male, in whom magnetic resonance imaging revealed enhancing lesions in the brain and spinal cord, accompanied by severe neurological symptoms. Despite intensive treatment, his condition deteriorated, and he died 5 months after the onset. At the initial consultation, no tick-bite sites were identified. However, interviews with the patient’s family revealed he had engaged in outdoor activities before disease onset. Based on the clinical course, epidemiological history, and detection of anti-TBEV antibodies, the patient was diagnosed with TBE. During hospitalization, serum neutralizing antibody titers gradually decreased but remained extremely high for 5 months. This case underscores the importance of epidemiological investigation, including history-taking for possible tick exposure, and highlights the need to raise awareness of tick-borne diseases among healthcare workers, particularly in endemic areas.

In Japan, nationwide surveillance of acute respiratory infections (ARI) was launched in April 2025, enabling monitoring of multiple respiratory pathogens. Human parainfluenza virus type 3 (HPIV3) is an important cause of respiratory infections. In 2025, HPIV3 increased from spring to summer, and Japanese media raised concerns about the emergence of a novel pathogen because public surveillance data on HPIV3 trends had not previously been available. In this study, phylogenetic analysis of HPIV3 isolates obtained in eastern Japan in 2025 was performed using nearly complete genome sequences. The isolates were grouped within previously circulating clusters (C1 and C2), and several sequences were closely related to viruses detected in Fukushima between 2018 and 2024, suggesting continued circulation of HPIV3 within the same geographic region (Fukushima Prefecture and surrounding areas), although broader circulation cannot be excluded. Some sequences were related to strains reported outside Japan, suggesting possible introduction from abroad. Overall, the sequences were highly similar and no distinct lineage forming a new cluster was observed. These findings indicate that the HPIV3 strains detected in 2025 belong to previously circulating lineages and do not represent the emergence of a new lineage.

The global COVID-19 pandemic caused substantial psychological burden, resulting in a 25% increase in the prevalence of anxiety and depressive disorders worldwide. This study examined factors associated with the multifaceted fear of COVID-19 among South Korean adults, providing crucial insights for culturally tailored public health interventions. We utilized a cross-sectional secondary data analysis from the 2022 Korea Community Health Survey (n = 228,470) and the Korean Statistical Information Service. Using multilevel linear regression, we evaluated three pre-specified primary community-level hypotheses: the proportion of one-person households, the density of internal medicine clinics by jurisdiction, and unmet healthcare needs. Results revealed that a higher proportion of one-person households correlated with increased fear, while a greater density of internal medicine clinics by jurisdiction was linked to reduced fear. To estimate these community-level associations, we adjusted for individual-level covariates. Exploratory analyses of these covariates suggested that factors such as female sex, older age, higher education, living with a spouse, economic activity, and better self-rated health were associated with heightened COVID-19 fear. These findings emphasize the need for culturally sensitive mental health support, community-based initiatives, and strategic healthcare resource allocation in Asian communities to strengthen resilience during future health crises.

There is no clear consensus regarding the optimal strategy for preventing the spread of COVID-19 among hematopoietic stem cell transplantation (HSCT) units. We conducted a questionnaire survey of 16 Japanese HSCT units in the greater Tokyo area to investigate the actual infection control strategies for COVID-19 implemented during 2023. Four facilities (25.0%) conducted active screening tests when patients were admitted to the HSCT unit. Regarding the admission of recipients with a history of COVID-19, 10 facilities (62.5%) had no clearly defined rules; instead, decisions were made based on factors such as the patient’s symptoms, the local epidemic situation, clinical course, and absence of pneumonia. For current COVID-19 cases, 9 facilities (56.3%) set the standard isolation periods based on the number of days from the onset of symptoms. Microbiological retest results were used as a reference at 11 facilities (68.8%), and 6 facilities considered extended isolation periods with the retest results. Seven facilities (43.8%) implemented additional extended isolation management for recovered recipients who still required hospitalization. Although little is known about vulnerability to SARS-CoV-2 among HSCT recipients and there is potential selection bias due to the small sample size, this summary serves as a reference for reviewing infection control strategies.

This study aimed to serologically diagnose Brucella spp. and Francisella tularensis in patients presenting with overlapping clinical symptoms. A total of 467 serum samples were tested for antibodies against smooth Brucella spp., Brucella canis, and F. tularensis using Rose Bengal Plate Test (RBPT), Serum Agglutination Test (SAT), Microagglutination Test (MAT), and indirect ELISA (iELISA). Seropositivity for smooth Brucella spp. was 12.85% (60/467) by RBPT/SAT and 10.06% (47/467) by iELISA, with moderate agreement (κ = 0.505). The diagnostic titer-based (sole) seropositivity rate was 9.85% (46/467). For B. canis, seropositivity was 5.14% (24/467) by RBPT and 3.64% (17/467) by iELISA, showing substantial agreement (κ = 0.715). The sole seropositivity rate was 3.64% (17/467). For F. tularensis, both MAT and iELISA showed 3.64% (17/467) seropositivity, with moderate agreement (κ = 0.561), while the sole seropositivity rate was 3.43% (16/467). Co-seropositivity was observed in 1.07% (n= 5) of samples between B. canis RBPT and smooth Brucella iELISA, and in 4.07% (n= 19) between smooth Brucella spp. and F. tularensis. One sample (0.21%) was noteworthy, suggesting possible co-infection. These findings confirm the regional presence of brucellosis and tularemia and highlight the value of combining serological methods in patients with non-specific symptoms and low antibody titers.

Human sapoviruses (HuSaVs), which cause acute diarrhea worldwide, are genetically diverse and divided into four genogroups (GI, GII, GIV, and GV). These were further subdivided into 18 genotypes (GI.1-7, GII.1-8, GIV.1, GV.1, and -2). Among them, only one strain has been reported worldwide for GII.7 to date. This strain was detected during a fecal pathogen screening of outpatients with gastroenteritis in Kumamoto Prefecture, Japan in 2008. We established a virus stock panel of diverse HuSaV strains as bioresources for further virological characterization studies and successfully propagated multiple HuSaV strains using a human duodenum cell line, HuTu80, supplemented with conjugated bile acids. However, several HuSaV genotypes including GII.7 strain did not propagate under the tested conditions. This study reports the successful propagation of the HuSaV GII.7 strain in HuTu80 subcloned cells. The propagated virus is an additional bioresource. We further used scaled-up serially passaged progeny viruses as antigens for antiserum production and demonstrated differences in immunogenicity among the cell culture-propagated HuSaV GII strains.

Information regarding the disease burden of respiratory syncytial virus (RSV) infection among the elderly in Japan is limited. A comprehensive review of the medical records from January 1, 2002, to December 31, 2023, was conducted for adult cases of community-onset pneumonia encountered in routine clinical practice at a community hospital in Shiogama, Japan. The pneumonia case definition employed in this study, for pathogens including major respiratory viruses, required laboratory diagnosis supported by solid virological data, such as virus isolation or rising antibody titers, rather than merely gene detection. The results indicated that, before the emergence of the Coronavirus disease-2019 pandemic in 2020, RSV and influenza virus infections accounted for a substantial proportion (30% each) of the detected respiratory viruses, and RSV persisted as the second most prevalent virus, surpassed only by Severe Acute Respiratory Syndrome Coronavirus-2, even after the pandemic emerged. The mortality rate associated with RSV as a prognostic factor reached 5-10%, depending on the period. The temporal pattern of case emergence from June 2011 to March 2025 suggested that community-acquired RSV infections in children likely precede the occurrence of RSV pneumonia in adults.

The proportion of people who have anti-nucleocapsid (N) protein antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported as a surrogate for the proportion of previously infected individuals. This seroepidemiologic survey, conducted from 6 November 2023 to 19 January 2024, aimed to measure the levels of anti-N protein antibodies produced in the body by SARS-CoV-2 among residents over 18 years of age in Bizen City, Okayama, Japan. We evaluated the prevalence of SARS-CoV-2 antibodies in the target population at the time of the investigation and assessed changes over time among participants who had previously been infected. Of the 444 participants, a total of 235 (52.9%) were infected within one year. The seroprevalence of participants testing positive remained above 80% until four months post-infection, after which the number of people who remained positive declined rapidly. Six months after infection, around 10% of participants tested positive for anti-N protein antibodies, and this seroprevalence remained the same for up to one year post-infection. We demonstrated that the anti-N protein antibodies test is useful for identifying recently infected individuals for several months post-infection. We showed that it becomes increasingly difficult to detect past infections as time elapses since infection.

Zika virus (ZIKV) is a mosquito-borne orthoflavivirus that causes acute symptoms, such as fever and conjunctivitis. Aedes (Stegomyia) aegypti and Ae. (Stg.) albopictus are the primary and secondary vectors, respectively, although other Aedes species may also transmit ZIKV. Aedes (Ochlerotatus) japonicus, native to East Asia, has recently spread to North America and Europe; however, its potential in ZIKV transmission, particularly in Japanese populations, remains unclear. In our previous study, a low viral titer of ZIKV was detected in a single virus-challenged Ae. japonicus individual. In the present study, we increased the sample size and compared infection rates and viral titers among Ae. japonicus, Ae. aegypti, and Ae. albopictus following exposure to the ZIKV strain MR766. Cumulative infection rates of Ae. japonicus (18%) were lower than those of Ae. aegypti (71%) and Ae. albopictus (67%). Nonetheless, some Ae. japonicus individuals had higher viral titers than the challenge dose, indicating efficient replication. ZIKV RNA was also detected in 14% of the saliva samples at 10 days post-infection. These findings suggested that the Japanese population of Ae. japonicus could potentially serve as a vector.

We report a rare case of human brucellosis caused by Brucella suisbiovar 5 in a 75-year-old man from Nagano Prefecture, Japan. He had no history of immune disorders and presented with fatigue, left ankle pain, and swelling. Initial antimicrobial therapy for suspected cellulitis and tenosynovitis failed, leading to admission to our hospital. Imaging and synovial fluid analysis suggested septic arthritis with a periarticular abscess. Gram-negative rods were recovered from synovial fluid obtained via arthrocentesis of the left ankle joint. Although the isolate could not be identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using a MALDI Biotyper system, it was successfully identified as B. suisbiovar 5 using species-specific PCR and nine-locus multilocus sequence typing (MLST). The patient was successfully treated with surgical debridement and prolonged antimicrobial therapy. This is the third documented human case of B. suisbiovar 5 infection in Japan, all originating from Nagano Prefecture, suggesting a localized cluster. This case highlights the diagnostic challenges of brucellosis, the limitations of routine identification methods, and the biosafety concerns for clinical laboratories. Enhanced awareness and surveillance are warranted in regions with emerging cases.

Seasonal influenza viruses continuously evolve, and the composition of the seasonal influenza vaccine is reviewed by the World Health Organization twice a year due to antigenic drift in the viral hemagglutinin (HA) protein. A timely assessment of how well vaccine-induced antibodies react to circulating viruses remains warranted. Here, immunogenicity of reference split vaccines for the 2025/26 season in Japan was analyzed in a mouse model using a microneutralization (MN) antibody assay against circulating A(H1N1)pdm09, A(H3N2), and B/Victoria-lineage viruses. In Japan, the vaccine used in the 2025/26 season consisted of three virus strains: A/Victoria/4897/2022 (IVR-238) (H1N1)pdm09, A/Perth/722/2024 (IVR-262) (H3N2), and B/Austria/1359417/2021 (BVR- 26). Reduced MN reactivity was observed against the tested circulating viruses, including A/Tokyo/EIS11-980/2025 (H1N1)pdm09 (HA subclade D.3.1), A/Tokyo/EIS13-029/2025 (H3N2) (HA subclade J.2.3), A/Tokyo/EIS13-355/2025 (H3N2) (HA subclade K), and B/Kanagawa/AC2414/2025 (B/Victoria lineage, HA subclade C3.1), with MN titers at least four-fold lower than those for the corresponding vaccine strains. These isolates had several amino acid substitutions at the antigenic or glycosylation sites in HA compared to the vaccine strains. These findings provide early laboratory indication of decreased immunogenicity of the vaccine against specific circulating viruses during the 2025/26 season in Japan.

Mumps vaccination, which is routinely administered in many countries, is not covered by Japan’s national immunization program. Therefore, mumps epidemic occurs every 3 or 4 years in Japan due to a low vaccine coverage rate. To prepare for the next resurgence, we examined the immunity against mumps using neutralizing antibodies (NT) against vaccine strain (genotype B) and wildtype virus (genotype G), and mumps-specific enzyme immunoassay for immunoglobulin G (IgG). We enrolled 83 children admitted to the Kawasaki Medical Hospital for diseases other than mumps between April and December 2022. The positive rates of NT for both of wild type and vaccine type were lower (25 .3%) than that of IgG (38.5%). No significant difference among them. Though individual infection histories were not confirmed, the absence of any mumps epidemic during the coronavirus disease pandemic, Therefore, almost all enrolled children were unlikely to have been infected with mumps, that is, they might have acquired immunity only by voluntary vaccinations. Therefore, we evaluate the immunity for mumps in the real world at three novel points as follows, (1) to evaluate under non-national immunization program (2) to evaluate Hoshino vaccine strains (3) to evaluate both IgG and the other immunity.

This study aimed to increase the data on characteristics and predictors of pediatric hMPV infection severity. Children admitted with ARI symptoms between 2021 and 2025 and diagnosed with hMPV by molecular testing were included. Seventy-eight children were included, of whom 48.7% were female. Most admissions occurred during winter and spring (92.3%). The median age was 14.9 months (IQR, 7.5–54.7), and 84.6% were younger than 5 years. At least one underlying comorbidity was present in 41% of patients, most commonly chronic lung disease. Major symptoms were cough (83.1%), rhinorrhea (61%), fever (59.2%), and stridor (41.6%), and tachypnea/dyspnea was observed in 31.2%. Median leukocyte count was 10,020/mm³ (IQR, 6,200–13,860), and median C-reactive protein level was 7.5 mg/dL (IQR, 1.1–26). Infiltration on chest radiographic (58.7%) were predominantly reticulonodular. About half of the patients (55.1%) required hospitalization; 21.8% needed respiratory support, and 6.4% were admitted to the pediatric intensive care unit. The need for respiratory support was significantly higher in children with comorbidities (p = 0.025), mortality was 2.6%. HMPV is a significant cause of ARIs in small children, particularly during winter and spring. Underlying comorbidities are associated with increased disease severity.

This study examined pediatric tuberculosis (TB) cases in Osaka City from 2008-2023, focusing on diagnostic methods and molecular epidemiology using variable number of tandem repeats (VNTR) analysis and whole-genome sequencing (WGS). Among 29 children aged 0-14 years (notification rate: 0.04 per 100,000), three (10.3%) were born abroad, and five (17.2%) were born in Japan with source cases from foreign countries. Source cases were identified for 20 children (69.0%); 18 of these (90.0%) had smear-positive pulmonary TB. Seventeen children (58.6%) were identified through contact investigations, highlighting the crucial role of contact tracing and early detection. Diagnosing pediatric TB was challenging: 15 children (51.7%) were asymptomatic and 17 (58.6%) had culture-negative results. To enhance diagnostic accuracy, interferon-gamma release assays, chest computed tomography, and gastric aspirate examination for acid-fast bacilli are recommended. In pediatric TB cases with identified source patients, VNTR clusters were confirmed by WGS to be closely related. Among children without identified sources, four formed VNTR clusters, and WGS of one representative case revealed no epidemiological links. These findings highlight the need to integrate molecular and epidemiological investigations to clarify transmission routes. Overall, this research underscores the need to integrate diagnostic and epidemiological approaches for effective control of pediatric TB.

Disasters such as earthquakes create conditions that amplify the risk of ectoparasitic infestations due to overcrowding, disrupted sanitation, and limited hygiene resources. This study explores ectoparasite-related online search interests in Türkiye before and after the earthquakes of February 2023, offering insights into potential secondary health concerns during disaster recovery. Weekly Google Trends data on scabies, lice, bed bugs, ticks, and insect bites were extracted for Türkiye and its provinces. Relative search volumes (RSV) were analysed to compare two years pre- and post-earthquake periods. Statistical analyses included time series comparisons. Following the earthquake, RSV for scabies and bed bugs increased sharply, while lice RSV significantly declined; tick and insect bite queries maintained consistent seasonal cycles. Integrating digital epidemiology insights with field-based surveillance could enhance the early detection and response to outbreaks following disasters. Long-term monitoring should be included in surveillance systems.

We investigated the association between frequenting 3Cs (closed spaces, crowded places, and close-contact settings) and trust in information on COVID-19, to elucidate information sources affecting public preventive measures. Nonprobability quota sampling was used to recruit 2000 residents of Tokyo and 2000 from Osaka. The retrospective survey was conducted in April 2024. These participants responded to an online survey about two periods, with and without an emergency declaration. Multiple regression analyses were performed and standardized partial regression coefficients for the independent variables calculated. Without an emergency declaration, a negative association between frequenting 3Cs and trust in family/relatives and a positive association with daily conversation were observed. 3Cs anxiety was positively associated with trust in three sources: medical professionals, family/relatives, or television (TV). During the emergency declaration period, a negative association between frequenting 3Cs and trust and a positive association between 3Cs anxiety and trust in the three sources above were observed, while there was a positive association between frequenting 3Cs and trust in celebrities, weekly magazines, or social networking services. A mediation analysis showed that trust in medical professionals, family/relatives, or TV increased 3Cs anxiety, and frequenting 3Cs decreased in state of emergency situations.

Escherichia coli O157 and O26 are well-known Shiga toxin-producing E. coli (STEC) serotypes, but other serotypes such as O91, O103, O111, O121, O145, and O165 have also emerged as important public health concerns. PCR-based methods, such as multilocus variable-number tandem-repeat analysis (MLVA), are commonly used for rapid genotyping of STEC strains. However, MLVA requires analysis of numerous loci, some of which are serotype-specific, limiting its applicability across multiple STEC serotypes. In this study, we developed a PCR-based open reading frame typing (POT) method for genotyping diverse STEC serotypes. By detecting 22 ORFs using two multiplex PCR assays, STEC genotypes were determined based on the presence or absence of specific ORFs. Most STEC serotypes, except for O121, were classified with high discriminatory power (Simpson’s index: 0.95–0.98). STEC-POT represents a rapid, cost-effective, and broadly applicable molecular typing tool. It facilitates timely outbreak detection and enhances public health surveillance by enabling rapid molecular epidemiological investigations.

Safety procedures for entering and exiting suit-type Biosafety level 4 (BSL-4) laboratories are essential to minimize the risk of exposure to high-risk pathogens and prevent their release outside the facility. Exiting a BSL-4 laboratory particularly requires complete decontamination of the positive-pressure protective suit. A critical challenge in maintaining BSL-4 safety operations is effectively training personnel in proper decontamination techniques using chemical showers. In this study, we introduce a training method that evaluates decontamination efficacy using a colored cream as a visualized pseudo-contaminant. The colored cream successfully visualized the physical removal process achieved by the chemical shower, thereby enhancing the efficacy of decontamination training.

Urban wastewater is increasingly recognized as a major reservoir of antimicrobial resistance and horizontal gene transfer. From urban wastewater in Hanoi, Vietnam, we isolated a multidrug-resistant Pseudomonas guariconensis strain, KNHN1, resistant to most antimicrobials, including carbapenems and cephalosporins, but susceptible to cefiderocol; and intermediate to colistin. Whole-genome sequencing revealed two chromosomally integrated integrative and conjugative elements (ICEs): ICE_{PgKNHN1_KPC} (131 kb) carrying bla_KPC-2 and ICE_{PgKNHN1_NDM} (108 kb), carrying bla_NDM-1, both flanked by conserved 18-bp att sites in the tRNA^Gly loci and encoding MOB_H-type relaxases. Polymerase chain reaction and subsequent sequencing confirmed ICE excision from the chromosome and formation of circular intermediates. Conjugation to Pseudomonas putida KT2440 occurred at ~10⁻² frequency, producing transconjugants with ICE_{PgKNHN1_NDM} (~85%), ICE_{PgKNHN1_KPC} (~10%), or both, all showing broad range β-lactam resistance. Comparative analysis indicated that ICE_{PgKNHN1_NDM} has a highly conserved backbone across multiple species and often co-carries bla_PME-1 and other resistance genes. To our knowledge, this is the first report of chromosomally integrated bla_NDM‑1 and bla_KPC‑2 in P. guariconensis mediated by functional ICEs. These findings underscore the pivotal role of environmental bacteria as reservoirs of clinically significant resistance genes, and highlight ICEs as key drivers in the dissemination of carbapenem resistance.

This large-scale post-marketing surveillance study (163 sites; February 2022–May 2023) evaluated the real-world safety and effectiveness of a newly initiated nirmatrelvir plus ritonavir combination for patients with COVID-19 in Japan. The current study reports the safety evaluation. The observation period was 28 days after the last day of administration. The safety analysis set comprised 2829 patients (mean [standard deviation] age, 63.1 [18.0] years; mild COVID-19, 80.8%; ≥1 risk factor for progression to severe COVID-19, 97.3%). The most common reason for discontinuing follow-up was symptom improvement (17.1%). Adverse drug reactions (ADRs) were observed in 423 (15.0%) patients (incidence [%]): dysgeusia (6.7%), diarrhea (2.6%), taste disturbance (1.5%), nausea (1.2%), vomiting (0.5%), decreased appetite (0.5%), and rash (0.5%). The median times to onset and recovery of these ADRs were 1–2 days and 2–6 days, respectively. Serious ADRs were observed in 6 patients (0.2%). No new safety signals were observed. The study showed that nirmatrelvir plus ritonavir was well tolerated in Japanese patients with COVID-19 in a real-world clinical setting.

ClinicalTrials.gov number: NCT05263908

Early detection of leprosy is crucial since delayed treatment can result in deformities and impairments. Recombinase Polymerase Amplification (RPA) is an isothermal DNA amplification technique that amplifies DNA fragments at a single, moderate temperature using a mixture of recombinase enzymes. In this work, PCR-confirmed cases of leprosy (positive for Mycobacterium leprae DNA) were subjected to RPA targeting an in-house designed RLEP amplicon of 175 bp. Following amplification, the RPA amplicons were analysed using agarose gel electrophoresis and SYBR Green I. The RPA-based detection of M. leprae DNA can be achieved within 20 min at 39 °C. The analytical sensitivity of the test was 0.5 cells/µl when tested using purified M. leprae genomic DNA standards. The clinical performance of the RPA was evaluated using 28 DNA samples extracted from skin biopsies. This assay has greater potential for developing a quick, accessible and field-friendly method for the visual detection of M. leprae DNA.

Cefiderocol (CFDC) is a novel siderophore cephalosporin with a unique cell entry feature and a high stability against a wide range of β-lactamases. We conducted antimicrobial susceptibility testing on 89 clinical isolates of carbapenem-non-susceptible gram-negative bacilli (CNS-GNB) strains detected at our hospital, evaluating the efficacy of novel antibiotics including CFDC, ceftolozane/tazobactam, ceftazidime/avibactam, and imipenem/cilastatin/relebactam. The strains included were as follows, 21 carbapenemase-producing Enterobacterales (CPE), 40 carbapenem-resistant Pseudomonas aeruginosa (CRPA), and 28 Stenotrophomonas maltophilia. Carbapenemase production were detected using NG-Test^® CARBA 5. Carbapenemase genes were analyzed by PCR-sequencing and extended-spectrum β-lactamase (ESBL) genes were detected by PCR. CPE isolates produced 17 IMP-, 3 NDM-, and one KPC-type carbapenemases, and 12 out of 21 CPE isolates produced ESBLs. All 40 CRPA did not produce carbapenemases. All 21 CPE isolates and 95% of CRPA were susceptible to CFDC. Colistin were intermediate against all CPE and 92.5% of CRPA isolates. In S. maltophilia isolates, susceptibility to CFDC and trimethoprim-sulfamethoxazole were 100% and 89.3 %. Although non-susceptibility to CFDC appeared in 2 CRPA isolates, MIC₉₀ of CFDC was within susceptible range against all three groups of clinical isolates. CFDC showed significant promise as a treatment option for infections caused by CNS-GNB.

The aim of this study was to determine the prevalence and persistence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) carriage among hospital food handlers. A prospective, single-center study was conducted in Sagamihara, Japan, from July to December 2021. Residual fecal specimens from routine examinations of 119 hospital food handlers were analyzed for ESBL-E and carbapenem-resistant Enterobacteriaceae (CRE). ESBL-E were detected in 32 isolates from 11 participants (9.2%), with Escherichia coli as the predominant species and a mean monthly positivity rate of 4.48%. The frequency of ESBL-E carriage was higher in individuals younger than 40 years of age (17.5%) than in those aged 40 years or above (5.1%). Highly homologous strains were detected within and between participants; the most common resistance genes were bla_CTX-M-1 group and bla_CTX-M-9 group. Six participants showed persistent ESBL-E carriage but CRE was not detected. These findings suggest that ESBL-E carriage is common among hospital food handlers, particularly among younger individuals, highlighting the need for enhanced surveillance and targeted hygiene interventions to limit ESBL-E transmission in healthcare food services.

Ensitrelvir is a novel antiviral drug that has been evaluated for its effectiveness against Coronavirus disease 2019 (COVID-19). This study aims to gather relevant evidence regarding the efficacy and safety of ensitrelvir in patients diagnosed with COVID-19. A systematic search was conducted in databases including PubMed, the Cochrane Library, Web of Science, and Scopus to identify pertinent studies on ensitrelvir's role in COVID-19 treatment up to September 2024. Nine studies were included in the analysis, comprising two retrospective studies, two phase 1 trials, three phase 2/3 trials, and two phase 3 trials. The findings indicated that ensitrelvir is associated with a reduced risk of death and shorter hospital stays for COVID-19 patients compared to control groups. Additionally, ensitrelvir demonstrated the ability to lower SARS-CoV-2 viral titers and RNA levels while accelerating the time to viral clearance compared to placebo. Reported adverse events were predominantly mild, with no serious adverse events noted. Ensitrelvir exhibited consistent pharmacokinetics across different populations, eliminating the need for dose adjustments. Ensitrelvir appears to be an effective and safe option for managing mild to moderate COVID-19 infections. However, further studies are needed to establish its efficacy and safety in treating COVID-19.