Japanese journal of infectious diseases最新文献

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.

During the COVID-19 pandemic, Mycoplasma pneumoniae infections were rarely observed in Japan, but a significant outbreak occurred in 2024. At Oita Children's Hospital, a rapid quenching probe polymerase chain reaction (QP-PCR) method was employed to detect the pathogen and to determine the prevalence of macrolide resistance. Between April 1 and September 30, 2024, we tested 679 patients - 462 (68.0%) were positive and 399 (86.4%) were macrolide resistant. The resistance rate was among the highest reported in Japan and comparable to those in neighboring Asian countries. Inpatients were younger than outpatients, and their diagnoses required longer periods of time; corticosteroids were used in 86% of hospitalized cases. QP-PCR detects common A2063G and A2064G mutations and provides results within 40 minutes, which could promote timely therapy, and this is true particularly in the case of younger children whose options could be limited. Early administration of effective antimicrobial agents is crucial for the control of macrolide-resistant M. pneumoniae. These findings indicate that QP-PCR-based diagnostics could significantly contribute to the management and control of M. pneumoniae outbreaks.

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.

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.

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.

Dengue virus (DENV), a mosquito-borne flavivirus, has emerged as a major global public health concern, with outbreaks occurring with increasing frequency worldwide, including in India. Laboratory confirmation is essential for accurate diagnosis, effective clinical management, and timely public health response. Real-time PCR (RT-PCR) is recognised as a sensitive and specific method for early diagnosis. This study evaluated the performance of the NeoDX Dengue Virus Screening Real-Time PCR Kit (NeoDX, Bengaluru, India), a pan-DENV assay, against the CDC DENV 1-4 RT-PCR assay. RNA extracted from 51 sera, obtained from suspected dengue cases, was tested by both assays. Of the 51 samples, 23 were positive by the CDC assay (DENV-1: 6, DENV-2: 4, DENV-3: 10; DEN-4:3). The NeoDX Dengue Virus Screening Real-Time PCR detected 24 positive samples, including all 23 positive samples by CDC assay, yielding a sensitivity of 100% and specificity of 96.4%. The Kappa value (0.961; 95% CI: 0.88-1.0) indicated very good agreement, supporting NeoDX Dengue Virus Screening Real-Time PCR as a reliable assay for early DENV detection.

The potencies of domestic influenza virus reference antigens were initially calibrated with a single radial immunodiffusion (SRID) assay using primarily prepared international reference antigens. The SRID potency should not be affected when using another reference antigen calibrated with the same international antigen. However, the SRID potency of test antigens can vary, although the causes of these discrepancies remain unclear. Here, we calibrated two candidate reference antigens (Lot A and Lot B) in the A(H3N2) subtype with various pairs of reference reagent sets (antigen and antiserum). The potencies of Lot A and Lot B varied depending on the reagent pair used, with a more pronounced effect in Lot A (CV = 5.4% vs. 3.8%). To explore the cause of these divergences, we analyzed the dissociation constant of each reagent pair and scored them based on the hypothesis that pairs exhibiting stronger antigen-antibody binding would have smaller precipitin rings. Comparing these scores with the respective potency scores, we observed a strong correlation between the Binding score (relative BLI-K_D) and potency score in Lot A (r = 0.8464, p = 0.0001) but not in Lot B (r = 0.4000, p = 0.1408). These data suggest that antigen-antibody binding strength is an influencing factor of SRID potency.

Mpox is a viral zoonosis caused by the monkeypox virus (MPXV), a double-stranded DNA virus mostly transmitted by direct contact, respiratory droplets, and contaminated fomites. Immunodeficiency, younger age, chronic diseases, and lack of immunization are all associated with severe illness. Mpox was declared by the World Health Organization to be a public health emergency of international concern on July, 2022. This report aimed to provide detailed histopathological and immunohistochemical findings of a fatal case of an immunosuppressed patient infected with MPXV, reported in Colombia in September 2022. A description of the clinical findings was made, followed by histopathological, immunohistochemical, and molecular studies to confirm the presence of MPXV genomes and viral antigens in different tissues. MPXV viral DNA of the clade IIb was identified, and MPXV genomes were found in the liver, lung, heart, and brain. Interestingly, MPXV antigens were observed in the skin and lungs, mainly in necrotic areas surrounded by active inflammatory cell markers. The simultaneous use of several diagnostic tools, such as histopathological, molecular, and next-generation sequencing, in fatal cases involving a variety of viral agents provides information that aids the understanding of the pathogenesis and clarifies the cause of death of this emerging infectious disease.

Corynebacterium mucifaciens, usually isolated from sterile human specimens, is a rare Corynebacterium species. We describe a blood-origin C. mucifaciens isolate that was resistant to macrolides/lincosamides and had been isolated from a patient with diabetic gangrene. This isolate formed mucoid colonies harboring a fragment of erm(X). As an initial antimicrobial, piperacillin/tazobactam was intravenously administered to the patient for two weeks. Gangrene debridement resulted in good local management. The clinical course was uneventful. The subculture from blood on a blood agar plate revealed mucoid colonies with a positive string test. Gram staining revealed the presence of a mucoid layer around the coryneform. The minimum inhibitory concentrations determined using the broth microdilution method indicated resistance to erythromycin/clindamycin. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), 16S rRNA gene sequencing, and antimicrobial resistance (AMR) gene profiling were performed. MALDI-TOF-MS identified this isolate as C. mucifaciens based on its high score (2.22). 16S rRNA gene sequencing revealed 99.3% similarity with DMMZ 2278(T) 16S rRNA gene sequence. AMR gene profiling revealed that this isolate possessed a fragment identical to that of erm(X) from Actinotignum schaalii. MALDI-TOF-MS with 16S rRNA gene sequencing can make it easier to identify C. mucifaciens when the coryneform has a mucoid colony appearance with hyperviscosity.

Currently, the mumps vaccine is not routinely recommended in Japan. Adding the mumps vaccine to the routine vaccination program requires an accurate estimation of the mumps viral infection disease burden. However, no precise estimate exists in Japan because mumps surveillance is sentinel surveillance with a reporting definition consisting only of a clinical diagnosis (parotid swelling). Since parotid swelling can be caused by pathogens other than the mumps virus, the estimation of mumps cases using the current surveillance data is inaccurate. To accurately ascertain the burden of disease, we estimated the burden using the results of tests performed at a single sentinel site for laboratory-based surveillance during the mumps endemic (Week 14, 2015, to Week 13, 2016) in Kanazawa. The estimated number of mumps cases based on laboratory-confirmed cases was 3,881 (95% confidence interval: 3,404-4,357), approximately 1,000 cases fewer than the estimated number based on clinically compatible mumps cases. Although the estimated number of mumps cases based on laboratory-confirmed cases was less than that of clinically compatible cases, the frequency of hearing loss due to mumps could potentially be 40% higher than that currently reported. To make the argument for routine mumps vaccination, surveillance using diagnostic testing information is important.