Antibiotic treatment is critical for individuals infected with gonorrhea and preventing disease transmission. This study aimed to analyze the antimicrobial susceptibility and molecular epidemiological characteristics of Neisseria gonorrhoeae isolates in Changsha, China. A total of 271 N.gonorrhoeae isolates collected from the clinical laboratories of two hospitals between 2016 and 2021 were analyzed for antimicrobial susceptibility using the agar dilution method. N. gonorrhoeae multi-antigen sequence typing (NG-MAST) was conducted for genotyping, and phylogenetic analysis was performed using the porB and tbpB sequences. The results showed that antimicrobial resistance against ciprofloxacin, tetracycline, and penicillin was high, and these drugs are no longer recommended for the treatment of gonorrhea. All isolates were susceptible to spectinomycin. However, in 2016–2021, a total of 15 (5.5%) ceftriaxone (CRO)-resistant strains and 31 (11.4%) isolates with decreased susceptibility to CRO were found, and the resistance rate to azithromycin had reached 7.1% in 2016–2017. Epidemiologically, the mosaic penA allele was identified in all CRO-resistant isolates. Based on NG-MAST, ST5061 was the most prevalent ST. Phylogenetic analysis suggested that the resistant isolates did not cluster independently. Despite focus on the local situation, this study raises the need for better gonorrhea medication and highlights that CRO may not be adequate as first-line treatment for gonorrhea in Changsha.

MenACYW-TT is a quadrivalent meningococcal tetanus toxoid-conjugate vaccine designed to prevent invasive meningococcal disease. The primary objective of this study was to demonstrate non-inferiority of the vaccine seroresponse to a single dose of MenACYW-TT compared with MCV4-DT, a licensed meningococcal quadrivalent diphtheria-conjugate vaccine. This Phase III double-blind, multicenter trial was conducted in meningococcal vaccine-naïve individuals aged 2–55 years in Japan (NCT04368429; jRCT2080225192). Participants were randomized 1:1 to receive either MenACYW-TT (n = 180) or MCV4-DT (n = 180). Functional antibodies against meningococcal serogroups A, C, W, and Y were measured using a serum bactericidal antibody assay with human complement (hSBA) at baseline (D0) and 30 days after vaccination (D30). Seroresponse was defined as a post-vaccination titer ≥1:16 in participants with a baseline titer <1:8; or a ≥4-fold increase in titer in participants with a baseline titer ≥1:8. Safety data were collected for 30 days. Non-inferiority of the seroresponse to MenACYW-TT vs. MCV4-DT was demonstrated on D30 for each serogroup tested (A: 85.6% vs. 65.4%; C: 96.6% vs. 62.6%; W: 87.4% vs. 49.2%; Y: 97.7% vs. 63.5%). MenACYW-TT was well tolerated with no safety concerns identified. A single dose of MenACYW-TT was well tolerated, with a non-inferior seroresponse compared with MCV4-DT. MenACYW-TT could thus be used as an alternative vaccine in meningococcal vaccine-naïve individuals.

The development of a vaccine against human respiratory syncytial virus (HRSV) has been hampered by enhanced respiratory disease due to the Th2-biased immune response. In the present study, MA103 and aluminum phosphate (Adju-Phos) adjuvants were used to verify the immunogenicity of the recombinant fusion (RBF) protein (F protein expressed by Escherichia coli). Both adjuvants significantly increased the neutralizing antibody titer and number of interferon gamma (IFN-γ)-secreting CD4+ T cells in mice. Based on the immunoglobulin G1 (IgG1)/IgG2a and IFN-γ/interleukin 4-secreting CD4+ T cell ratio, however, MA103 significantly enhanced the Th1-biased immune response. The pathological damage to the lung in the RBF/MA103 group was less than what was seen in the RBF/Adju-Phos group. Additionally, the number of HRSV copies in the lungs of the RBF/MA103 group decreased by approximately 3 × log₁₀. These results suggested that MA103 provides better protection against HRSV in mice.

We aimed to study the effects of a methyltransferase 3 (METTL3) inhibitor on osteomyelitis. Bone marrow cells (BMs) and peripheral blood mononuclear cells (PBMCs) were isolated from osteomyelitis patients at our hospital. Primary BM-derived macrophages (BMDMs) were incubated with lipopolysaccharide (LPS), poly(I:C), or PAM3CSK4 after pretreatment with STM2457. S. aureus was injected into the intramedullary canal to construct an osteomyelitis C57BL/6 mice model, which was then treated with STM2457. Body weights, μCT three-dimensional analyses, and bacterial burdens of the mice were obtained. Up-regulated METTL3 expression was found in both BMs and PBMCs of osteomyelitis patients. LPS and PAM3CSK4-induced IL-6 and TNF-α secretion in BMDMs could be inhibited by STM2457 pretreatment, while STM2457 pretreatment did not affect the relative expression of NOS2, IL-6, and TNF-α after incubation with poly(I:C). STM2457 alleviated the symptoms of osteomyelitis in mice with increased body weights, diminished reactive bone formation and cortical bone loss, increased bacterial burdens, and decreased IL-6 and TNF-α secretion. STM2457 pretreatment down-regulated the relative expression of myeloid differentiation factor 88 (MyD88), p-TAK, and p-IKKα/β in LPS-stimulated BMDMs, while it did not show any effect on poly(I:C)-stimulated BMDMs. STM2457 alleviates the onset of osteomyelitis in mice by down-regulating the relative expression of MyD88 and NF-κB relevant inflammation molecules in macrophages.

Receptor-interacting serine/threonine kinase (RIPK) is associated with cellular inflammation and immune regulation. The current study explored the role of RIPK2 in osteomyelitis and the potential upstream targets of RIPK2. A Staphylococcus aureus-induced osteomyelitis mouse model was established using wild-type (WT) and ubiquitin-specific peptidase 8 (USP8)-deficient (USP^-/-) mice, and the osteomyelitis-related symptoms were evaluated. Bone marrow-derived macrophages (BMDMs) were isolated from the WT and USP^-/- mice. Enzyme-linked immunosorbent assays, quantitative polymerase chain reaction, and immunoblot analysis were used to determine the levels of target biomarkers, which were induced by lipopolysaccharide (LPS), CpG, or PAM3CSK4. USP8 promoted RIPK2-mediated NF-κB activation. USP8 is indispensable for RIPK2-mediated LPS-induced NF-κB activation in BMDMs. USP8 is required for the production of inflammatory cytokines induced by LPS, CpG, or PAM3CSK4 in BMDMs. In addition, USP^-/- mice exhibited ameliorated symptoms, including less body weight and cortical bone loss, and reduced bacterial load and reactive bone formation in the S. aureus-induced osteomyelitis mouse model. USP8 is critical in the S. aureus-induced osteomyelitis mouse model by targeting RIPK2 ubiquitination.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2021 and gradually overtook the Delta variant, which was the predominant variant at that time. The Omicron variant has been consecutively replaced by related sublineages. The real-time RT-PCR assays developed by the National Institute of Infectious Diseases (NIID), Japan (i.e., the NIID-N2 and NIID-S2 assays) are the reference assays that have been used in Japan since the outbreak of SARS-CoV-2. To evaluate the applicability of the NIID assays for the Omicron variants, trends in the prevalence of nucleotide mismatches in the primer/probe sequences were traced using sequences registered in the Global Initiative on Sharing Avian Influenza Data database. Approximately 99% of the deposited Omicron variant sequences did not have any mismatches in the NIID assay primer/probes from January to August 2022. This indicates that the NIID assays have been able to detect the changing SARS-CoV-2 Omicron variants.

In 2012, Escherichia fergusonii harboring a heat-labile enterotoxin (LT) was isolated from healthy chickens in South Korea. However, little is known regarding the prevalence, spread, and pathogenicity of these strains in humans and animals. This study aimed to understand the public health threats, such as the distribution, antimicrobial resistance, and genetic diversity of E. fergusonii carrying LTs. E. fergusonii containing LT was isolated from 15.0% (52/346) of chicken fecal samples from all three tested chicken farms but not from 360 pig fecal samples. The antimicrobial susceptibility testing revealed that over 75% of strains were resistant to ampicillin, kanamycin, nalidixic acid, streptomycin, or tetracycline; additionally, 71.2% (37/52) of strains were resistant to all five of these antimicrobials. The 52 strains were clustered into eight pulsed-field gel electrophoresis (PFGE) types, with types V and type VI accounting for 84.6% (44/52). In the present study, multiple chicken farms harbored E. fergusonii with similar antimicrobial resistance patterns and genetic clonality. Since the pathogenicity of LT-bearing E. fergusonii in humans and animals, such as food poisoning and sporadic diarrhea via meat, the transmission of the strains, and the dissemination of antimicrobial resistance genes are unknown, additional research is required.

Severe fever with thrombocytopenia syndrome (SFTS) is caused by the severe fever with thrombocytopenia syndrome virus (SFTSV). Although SFTS is a fatal tick-borne zoonosis, it can infect humans without tick bite exposure. Recently, direct transmission of SFTSV from companion pets to humans has become a major problem. We present a case of SFTSV transmission from a dead community cat to a woman who buried the cat in Miyazaki Prefecture, Japan. The community cat died without a diagnosis of SFTS, and the woman buried it without taking any precautions. She developed symptoms of SFTS 9 days later. The woman tested positive for SFTS viral RNA and anti-SFTSV antibodies. The cat’s carcass was exhumed, and tissue samples were collected to confirm the viral infection. Numerous copies of viral RNA were detected. The SFTSV M segment sequences in the cat and the woman were 100% homologous. The woman claimed that she had touched blood that had leaked from the cat’s body while burying it. However, she could have been infected while transporting the cat to the animal hospital. This study highlights the risk of SFTSV infection from contact with sick or dead community cats.

Mobile digital chest radiography (CR) is a commonly used method for pulmonary tuberculosis (PTB) screening among homeless people in Nishinari District, Osaka City, Japan. We investigated mobile CR screening (MCS) to calculate the case-finding rate of culture-confirmed PTB among homeless examinees in Nishinari District from 2013 to 2019. PTB was defined as a sputum culture-confirmed case. Examinees with culture-confirmed PTB >90 days after MCS were defined as having no progression to active tuberculosis when undergoing MCS. We collected participants’ information, including their name, date of birth, age, sex, date of MCS, CR classification (whether the abnormal CR result required further investigation), date of PTB diagnosis, and sputum smear results. Of 10,111 homeless people, 175 (1.7%) with abnormal CR results underwent further investigation at medical facilities. Of those with abnormal CR results, 22 (0.22%) were diagnosed with culture-positive PTB within 90 days of MCS. Of 22 PTB cases with culture-positive results, 13 (59.1%) were smear-positive. We found that MCS contributed to the detection of PTBs with a lower smear-positive rate among patients with PTB analyzed by MCS compared with all culture-confirmed PTB cases in Nishinari District.