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 M113SNPs lineage has gained predominance as the cause, surpassing both the ancestral M1global and globally prevalent hypervirulent M1UK lineages. M113SNPs specifically harbored speC, spd1, and sdaD2; the latter was also present in most of M1UK. Furthermore, M113SNPs 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 M113SNPs lineage, which possesses distinctive genetic features and may have undergone localized evolutionary adaptation.
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 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 blaCTX-M (94%), while all CRE carried blaNDM and blaOXA-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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
