Japanese journal of infectious diseases最新文献

Influenza A/(H1N1)pdm09 virus evolves through continuous antigenic variation in both surface antigens, such as hemagglutinin (HA) and neuraminidase (NA) proteins, which affect its pathogenicity, the effectiveness of the host immune response, and drug resistance. This study reports the evolution and dynamics of 527 HA protein sequences of influenza A/(H1N1)pdm09 Indian isolates submitted from 2009 to 2020. These isolates were aligned with a reference sequence and 22 sequences representing different clades using MEGA X, and subjected to phylogenetic analysis. The strains were predominantly grouped in clades 6B.1 and 6B.2. Prediction of glycosylation sites using the BioEdit and NetNglyc servers showed 12 glycosylation sites distributed in both the stem and globular head regions of HA. Functional evaluation showed that there were 22 deleterious mutations that could affect the function of HA. In addition, 403 unique mutations were distributed across various isolates, indicating the dynamics of antigenic variation in Indian isolates. These results provide an understanding of the frequency, phylodynamics, and impact of mutations in Indian isolates of influenza A/(H1N1)pdm09 relative to global isolates. Monitoring the genomic evolution of the virus will support studies on strain selection for vaccine development and devising control and prevention measures to manage this respiratory infection.

Human rhinovirus (HRV) infections are generally referred to as the common cold, and are the main cause of mild symptoms. HRV is less frequently implicated in the development of severe respiratory infections. This study reports a nosocomial outbreak of bronchitis and pneumonia caused by HRV in a hospital during the COVID-19 epidemic in September 2022 in Gunma Prefecture, Japan. The patient continued to be symptomatic for nine days. During this outbreak, all 15 residents displayed respiratory symptoms. HRV-A was detected in 12 of the 12 samples, and phylogenetic analysis classified the strain as HRV-A type 61. HRV, COVID-19, and other respiratory infections cannot be differentiated based solely on clinical symptoms. A surveillance system to monitor them is thus needed.

Sapovirus (SaV) infections are a public health problem because they cause acute gastroenteritis in humans of all ages, both sporadically and as outbreaks. However, only a limited amount of SaV sequence information, especially whole-genome sequences for all the SaV genotypes, is publicly available. Therefore, in this study, we determined the full/near-full-length genomic sequences of 138 SaVs from the 2001 to 2015 seasons in 13 prefectures across Japan. The genogroup GI was predominant (67%, n = 92), followed by genogroups GII (18%, n = 25), GIV (9%, n = 12), and GV (6%, n = 9). Within the GI genogroup, four different genotypes were identified: GI.1 (n = 44), GI.2 (n = 40), GI.3 (n = 7), and GI.5 (n = 1). We then compared these Japanese SaV sequences with 3,119 publicly available human SaV sequences collected from 49 countries over the last 46 years. The results indicated that GI.1, and GI.2 have been the predominant genotypes in Japan, as well as in other countries, over at least four decades. The 138 newly determined Japanese SaV sequences together with the currently available SaV sequences, could facilitate a better understanding of the evolutionary patterns of SaV genotypes.

Sapovirus (SaV) and astrovirus (AstV) are important viral causes of acute gastroenteritis. From 2016 to 2019, 172 stool samples were collected from children with gastroenteritis in Kobe, Japan for sentinel surveillance of infectious gastroenteritis. In this study, we tested 53 of the 172 stool samples that tested negative for other enteric viruses to determine the prevalence of SaV and AstV. The samples were screened for SaV and AstV using real-time polymerase chain reaction. Positive samples were genotyped by sequencing and genetic analysis of partial regions of the capsid and RNA-dependent RNA polymerase. Of the 53 samples tested, 19 (35.8%) were positive for SaV, and three (5.7%) were positive for AstV. Of the total samples, 11.0% (19/172) and 1.7% (3/172) were positive for SaV and AstV, respectively. The most frequently detected genotype of SaV was GI.1, followed by GII.3. The AstV genotypes were MAstV1.1 and MAstV1.4. This study indicates that SaV and AstV are important causes of viral gastroenteritis in children.

Osteomyelitis is the infection and destruction of the bone. To date, there is no universal protocol for its treatment. Receptor-interacting serine/threonine-protein kinase 2 (RIPK2) has been implicated in osteomyelitis development. However, the detailed mechanism remains unknown. Here, 6-8w wild-type or Pellino E3 Ubiquitin Protein Ligase Family Member 3 (Peli3)-deficient mice were injected with Staphylococcus aureus to induce osteomyelitis. RAW264.7 cells or bone marrow-derived macrophages isolated from mice were treated with lipopolysaccharide (LPS). Knocking down Peli3 in RAW264.7 cells increased the expression of inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-α) after LPS stimulation. Inflammation was also activated in S. aureus-induced Peli3-deficient mice. Moreover, S. aureus-infected Peli3-deficient mice also displayed more severe symptoms of osteomyelitis than S. aureus-infected wild-type mice. Moreover, Peli3 targets and degrades RIPK2 through K48-linked ubiquitination, and negatively modulates osteomyelitis by degrading RIPK2. Our data further expands the current understanding of RIPK2 in osteomyelitis, and suggests that RIPK2 might serve as a novel therapeutic target for treating osteomyelitis.

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infections (ALRTIs). In this study, we aimed to evaluate the role of viral load, cytokines, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) in determining the severity of RSV disease and identify potential biomarkers of disease severity. A total of 142 patients with RSV infection (aged between 2 months and 5 years) who presented with ALRTI between December 2013 and March 2016 were enrolled. Their nasopharyngeal aspirates were subjected to RSV viral load quantification, and local cytokine levels of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), IL-17A, interferon γ (IFN-γ), and IL-10 were determined using a cytokine bead array. The levels of MMP-9 and TIMP-1 in 109 aspirates were calculated using Quantikine ELISA. These parameters were compared for different disease severity categories. A higher viral load and increased levels of TNF-α, MMP-9, and MMP-9:TIMP-1 were associated with greater severity of disease; whereas levels of IL-17A, IFN-γ, and IFN-γ:IL-10 were associated with disease resolution. When defining the transition from non-severe to severe disease, MMP-9 had a sensitivity and specificity of 89.7% and 85.4%, respectively. Moreover, MMP-9:TIMP-1 had a sensitivity and specificity of 87.2% and 76.8%, respectively. Hence, MMP-9, MMP-9:TIMP-1, TNF-α, and IL-10 could serve as potential biomarkers for disease progression in RSV-infected children.

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.

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.

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.

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.