Comparison of self-reported symptoms in COVID-19 patients who had or had not previously received COVID-19 mRNA vaccination.

Although mRNA coronavirus disease 2019 (COVID-19) vaccines have been reported for high effectiveness against symptoms, it remains unclear whether post-vaccination infections are less symptomatic than infections in vaccine-naive individuals. We included patients with COVID-19 diagnosed by polymerase chain reaction tests during Japan's alpha and delta variant epidemics. COVID-19 symptoms at approximately 4 weeks were compared based on COVID-19 vaccination status. In total, 398 cases (372 symptomatic and 26 asymptomatic; 286 unvaccinated, 66 vaccinated with one dose, and 46 with two doses) were analyzed. The most common symptoms were fever (78.4%), fatigue (78.4%), cough (74.4%), loss of taste or smell (62.8%), and headache (59.8%). Post-vaccination infections were significantly less likely to be symptomatic. Possible confounder-adjusted odds ratios of two vaccine doses against fatigue, dry eyes and mouth, insomnia, fever, shortness of breath, unusual muscle pains, and loss of taste or smell were 0.18 (95% confidence interval [CI]: 0.09-0.38), 0.22 (95% CI: 0.08-0.59), 0.33 (95% CI: 0.14-0.80), 0.31 (95% CI: 0.15-0.63), 0.36 (95% CI: 0.16-0.76), 0.40 (95% CI: 0.19-0.82), and 0.44 (95% CI: 0.22-0.87), respectively. Post-vaccination infections after two mRNA COVID-19 vaccine doses show milder and fewer symptoms than infections in unvaccinated patients, highlighting the effectiveness of vaccination.

Real-World Effectiveness of the mRNA COVID-19 Vaccines in Japan: A Case-Control Study.

The real-world effectiveness of the coronavirus disease 2019 (COVID-19) vaccines in Japan remains unclear. This case-control study evaluated the vaccine effectiveness (VE) of two doses of mRNA vaccine, BNT162b2 or mRNA-1273, against the delta (B.1.617.2) variant in the Japanese general population in the period June-September 2021. Individuals in close contact with COVID-19 patients were tested using polymerase chain reaction (PCR). A self-administered questionnaire evaluated vaccination status, demographic data, underlying medical conditions, lifestyle, personal protective health behaviors, and living environment. Two vaccine doses were reported by 11.6% of cases (n = 389) and 35.2% of controls (n = 179). Compared with controls, cases were younger and had a lower proportion who always performed handwashing for ≥20 s, a higher proportion of alcohol consumers, and a lower proportion of individuals living in single-family homes or with commuting family members. After adjusting for these confounding factors and day of PCR testing by multivariate logistic regression analysis, the VE in the period June-July (delta variant proportion 45%) was 92% and 79% in the period August-September (delta variant proportion 89%). The adjusted VE for homestay, hotel-based isolation and quarantine, and hospitalization was 78%, 77%, and 97%, respectively. Despite declining slightly, VE against hospitalization remained robust for ~3 months after the second dose. Vaccination policymaking will require longer-term monitoring of VE against new variants.

[Evaluation of Accuracy and Availability of the Antimicrobial Resistance Testing by the Direct Disc Methods Using AmpC/ESBL Differential Discs in the Samples in Which Enterobacterales are Detected in Blood Culture].

The emergence and dissemination of drug-resistant Gram-negative bacilli have been recognized as a serious health concern in worldwide. The isolation rates of Extended-Spectrum ß-lactamases (ESBL) and AmpC ß-lactamases (AmpC) producing gram negative rods are increasing in our hospital. In the present study, we evaluate the availability of the antimicrobial resistance testing by the direct disc methods using AmpC/ESBL differential discs. One hundred and ten strains of Enterobacterales were isolated during the observation period, of which 19 strains (17%) were ESBL-positive and 6 strains (5%) were AmpC-positive. The positive and negative coincidence rate between direct disc methods and standard disc methods were 100%. We conclude that the direct disc method is a useful and rapid detection method for ESBL and AmpC from blood culture samples.

An essential role of N-terminal domain of copper chaperone in the enzymatic activation of Cu/Zn-superoxide dismutase.

Cu/Zn-superoxide dismutase (SOD1) is an enzyme that disproportionates superoxide anion into hydrogen peroxide and molecular oxygen. The enzymatic activity of SOD1 requires the binding of copper and zinc ions and also the formation of a conserved intramolecular disulfide bond. In a eukaryotic cell, a copper chaperone for SOD1 (CCS) has been known to supply a copper ion and also introduce the disulfide bond into SOD1; however, a mechanism controlling the CCS-dependent activation of SOD1 remains obscure. Here, we characterized CCS isolated from a human liver fluke, Clonorchis sinensis, and found that an N-terminal domain of CCS was essential in supplying a copper ion in SOD1. Regardless of the presence and absence of the N-terminal domain, CCS was able to bind a cuprous ion at the CxC motif of its C-terminal domain with quite high affinity (Kd~10-17). The copper-bound form of full-length CCS successfully activated C. sinensis SOD1, but that of CCS lacking the N-terminal domain did not. Nonetheless, the N-terminally truncated CCS with the bound copper ion was found to correctly introduce the disulfide bond into SOD1. Based upon these results, we propose that the N-terminal domain of CCS has roles in the release of the copper ion bound at the C-terminal domain of CCS to SOD1.

A molecular mechanism realizing sequence-specific recognition of nucleic acids by TDP-43.

TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA-binding protein containing two consecutive RNA recognition motifs (RRM1 and RRM2) in tandem. Functional abnormality of TDP-43 has been proposed to cause neurodegeneration, but it remains obscure how the physiological functions of this protein are regulated. Here, we show distinct roles of RRM1 and RRM2 in the sequence-specific substrate recognition of TDP-43. RRM1 was found to bind a wide spectrum of ssDNA sequences, while no binding was observed between RRM2 and ssDNA. When two RRMs are fused in tandem as in native TDP-43, the fused construct almost exclusively binds ssDNA with a TG-repeat sequence. In contrast, such sequence-specificity was not observed in a simple mixture of RRM1 and RRM2. We thus propose that the spatial arrangement of multiple RRMs in DNA/RNA binding proteins provides steric effects on the substrate-binding site and thereby controls the specificity of its substrate nucleotide sequences.

Clinical features of enterococcal bacteremia due to ampicillin-susceptible and ampicillin-resistant enterococci: An eight-year retrospective comparison study.

Enterococcus consists human bowel flora, but sometimes behave as an important nosocomial pathogen. In order to identify clinical characteristics that help discriminate between ampicillin-susceptible and ampicillin-resistant enterococcal bacteremia in advance for antimicrobial susceptibility testing, a retrospective eight-year study was carried out in patients with enterococcal bacteremia experienced in Saga University Hospital, Japan. A total of 143 patients were included in the analysis: 85 (59.4%) with bacteremia caused by ampicillin-susceptible enterococci and 58 (40.6%) by ampicillin-resistant strains. Hospital-acquired bacteremia was present in 79.0% (113/143) of patients. Abdominal infections, urinary tract infections, and unknown source were predominant foci for the two groups. Patients with ampicillin-resistant enterococcal bacteremia was significantly associated with hematological cancer, immunosuppressive therapy, prior use of antibiotics, and mucositis associated with febrile neutropenia. The 28-day mortality was significantly higher in ampicillin-resistant enterococcal bacteremia. On multivariate analysis, independent risk factors for ampicillin-resistant enterococci were as follows: prior exposures to penicillins and carbapenems, and bacteremia related to mucositis with febrile neutropenia. These findings would assist physicians in deciding whether glycopeptide antibiotics should be included as an empiric antibiotic therapy in patients with suspected enterococcal infections and also those with persistent neutropenic fever refractory to fourth generation cephalosporin. A few cases of MALDI-TOF MS-identified Enterococcus faecium that turned out ampicillin-sensitive were also described to emphasize the importance of taking epidemiological aspects of patients into considerations when deciding initial antimicrobial treatment.

Pertussis outbreak in university students and evaluation of acellular pertussis vaccine effectiveness in Japan.

BACKGROUND: Recent studies worldwide have reported increasing numbers of adults diagnosed with Bordetella pertussis despite receiving childhood vaccinations. This study describes a pertussis outbreak at a university medical faculty campus and examines the effectiveness of diphtheria, tetanus, and pertussis (DTaP) vaccination completed during infancy in Japan. METHODS: After the outbreak, self-administered questionnaires and serum samples were collected from students on campus to determine the incidence of pertussis and underlying diseases. Pertussis was diagnosed on the basis of clinical criteria and serum anti-pertussis toxin antibody levels. Using data collected from 248 first and second grade students who had submitted copies of their vaccination records, we evaluated the effectiveness of DTaP vaccination in infancy against adult pertussis. RESULTS: Questionnaire responses were obtained from 636 students (of 671 registered students; 95% response rate). Of 245 students who reported a continuous cough during the outbreak period, 84 (attack rate: 13.2%) were considered "probable" pertussis cases that met clinical criteria. The outbreak occurred mainly in first and second grade students in the Faculty of Medicine. Of 248 students who provided vaccination records, 225 had received 4 DTaP doses (coverage: 90.7%); the relative risk of the complete vaccination series compared to those with fewer than 4 doses or no doses for probable cases was 0.48 (95% confidence interval: 0.24-0.97). CONCLUSIONS: Waning protection was suspected due to over time. Booster vaccination for teenagers and development of highly efficacious pertussis vaccines are needed.

[Clinical and microbiological analysis of community-acquired bacteremia admitted to a tertiary teaching hospital].

OBJECTIVES: To investigate clinical and microbiological characteristics of community-acquired bacteremia (CAB). METHODS: We retrospectively analyzed subjects with CAB hospitalized at Saga University Hospital between January 2009 and September 2011. We investigated causative organisms, primary infection sites, and subject summaries and complications, and analyzed the mortality factor. RESULTS: CAB incidence was 185 cases, with 192 organisms cultured. Causative organisms were gram-positive bacteria in 81 strains (42%), 9 (11%) of which were methicillin-resistant Staphylococcus aureus (MRSA). Gram-negative bacteria were identified in 111 strains (58%), with 80% Enterobacteriaceae. Five of the 111 (5%) were caused by extended-spectrum beta-lactamase (ESBL) producing bacteria. The most frequent bacteremia portal was intraabdominal infection (29%, 54/185). During hospitalization of 1-180 days, 20 subjects eventually died. Neutropenia on admission was associated with significantly higher mortality than without (30% vs. 3%, p < 0.001). Septic shock rates were higher in non-survivors than survivors (45% vs. 14%, p = 0.002), and more complications were documented in non-survivors than survivors (50% vs. 25%, p = 0.017). No specific pathogen or primary infection site was associated with higher mortality. CONCLUSIONS: Antimicrobial-resistant pathogens such as MRSA and ESBL producers should be considered even in CAB, especially in subjects with healthcare-associated infection, regardless of how small the number. The CAB treatment course should consider subjects summaries, severity, and complications.

The importance of pharmacokinetic consultation of cefepime treatment for Pseudomonas aeruginosa bacteremia: a case report of severe thermal burn injury.

The patient is a 54-year-old man with severe thermal burn injury involving 45.5% of the total body-surface area, complicated with bacteremia caused by Pseudomonas aeruginosa with a cefepime MIC of 8 µg/ml. The plasma concentrations of cefepime 1 g every 6 h measured by validated high performance liquid chromatography were 25.8 µg/ml at 1 h and 6.28 µg/ml at 5 h after infusion, and 3.9 µg/ml before the infusion, when creatinine clearance was increased to 136 ml/min by vigorous fluid replacement. The pharmacokinetic-pharmacodynamic analyses in the one-compartment model with use of the Sawchuk-Zaske method revealed marked increase in the volume of distribution (28.9 l), total clearance (10.7 l/h), and shortening of plasma half- life (1.79 h) of cefepime, with time >MIC and 24-h area under the concentration-time-curve being 58% and 358, respectively. These pharmacokinetic parameters of cefepime quantified in the patient estimated a time >MIC of 87% if administered every 4 h. P. aeruginosa, however, was successfully eradicated without revision of the dosing regimen of cefepime. Decrease in creatinine clearance by correction of the fluid imbalance and wound closure by skin graft surgery likely contributed to the restoration of fluid shift, resulting in normal disposition of cefepime and favorable clinical outcome of the patient.

[Influenza virus infection: clinical diagnosis and current considerations].

Point-of-care diagnosis of influenza requires sound recognition of the prevalence of the signs and symptoms of the patients, which would help to define the pattern of clinical presentation of this infection. In severely ill patients, however, clinical features of influenza could be erroneously modified by the exacerbation of co-morbid conditions, resulting in a delay of the diagnosis. Enzymatic rapid diagnostic tests, although establishing the diagnosis with positive result especially when the virus is in high circulation, has relatively poor sensitivity for the 2009 A/H1N1 virus and it varies among the different age groups. Given the likelihood of long-term circulation of the novel H1N1 virus, patients' clinical features and the performance of the rapid tests should continuously be monitored.

[Quantitative Bayesian diagnosis developed for lower respiratory tract infections due to methicillin-resistant Staphylococcus aureus].

Using quantitative Bayesian analysis as a clinical epidemiological approach, we developed a diagnosis for lower respiratory tract infection (LRTI) due to Methicillin-resistant Staphylococcus aureus (MRSA). We retrospectively reviewed the charts of 181 subjects--a derivation cohort-with MRSA retrieved from lower respiratory specimens June 2006 to March 2008. Dividing them into infection or colonization (no infection) groups, we compared them for the presence or absence of clinical parameters, including fever > 38 degrees C, MRSA >106 CFU (colony-forming units)/mL, phagocytosis on Gram staining, serum albumin < 3.0 g/dL, and peripheral WBC count > 15,000/mL. We them determined positive and negative likelihood ratios (LR +, LR -) for these parameters to quantify MRSA-LRTI diagnostic probability based on combined likelihood ratios (Bayesian analysis). We then determined Bayesian MRSA-LRTI diagnostic probabilities (BDPs) in 40 subjects with respiratory MRSA--a validation cohort-from May 2008 to October 2008 clinically judged with either infection (n = 14) or colonization (n = 26) by infection control personnel (ICP) blinded to the test (parameter LR+ and LR -). BDPs (mean +/- SD) quantified by combining the four parameters-fever, MRSA CFU, phagocytosis, and serum albumin-were 62.3 +/- 25.4% for 14 judged with infection, and 40.2% +/- 20.4% for 26 patients judged with colonization (p = 0.005). Using a diagnostic probability of 51% as the cut off, we compared positive and negative predictive Bayesian diagnoses ICP judgment, i.c., 77% vs. 85%. The Bayesian approach proved useful in quantitatively diagnosing infectious disease such as MRSA-LRTI that lack established diagnostic, and may aid physicians in deciding the need for specific antimicrobial therapy.

[Acute respiratory distress syndrome induced by hydrogen fluoride gas inhalation].

A 21-year old man was referred to our hospital with severe respiratory distress and diffuse infiltrative shadows on chest radiograph. He had been exposed to irritant gas when polishing the inside of a stainless tank using a chemical cleaner containing hydrofluoric acid and nitric acid. He felt sick immediately after exposure and experienced respiratory distress within a few hours. He was successfully treated with intensive care including mechanical ventilation and administration of high dose methylprednisolone. Later, his illness was diagnosed as acute lung damage induced by hydrogen fluoride gas inhalation based on the findings of increased fluoride concentration in serum and urine specimen, and decreased serum calcium level.

Nocardiosis in adult-onset Still's disease and vasculitis syndrome.

Four cases of nocardiosis in patients with adult-onset Still disease and vasculitis syndrome are presented. Three patients developed lung abscesses and 1 case developed a brain abscess. All were treated with high-dose corticosteroids, and 3 were given cyclosporine when they developed nocardiosis. All patients were successfully treated with antibiotics; cyclosporine was discontinued in 2 cases. These cases indicate that systemic nocardiosis can develop in patients with various rheumatologic diseases who are treated with corticosteroid and immunosuppressive drugs such as cyclosporine.

Disseminated infection by Bipolaris spicifera in an immunocompetent subject.

We report a case of disseminated infection due to Bipolaris spicifera in an immunocompetent male. Histopathological studies of lymph node, lung, and liver biopsy specimens showed a dark pigmented, granular fungal structure inside the granuloma. The disease was accompanied by the unusual feature of positive lupus anticoagulant in serum and low-density areas expanding along the portal vein in the liver. The disease responded to combination therapy with intravenous amphotericin B and voriconazole, but recurred during oral itraconazole. The fungal isolate from the lymph node was identified as Bipolaris spicifera on the basis of morphology and molecular biological data.

[A case of pulmonary artery pseudoaneurysm secondary to lung abscess].

A 53-year-old man visited his family doctor complaining of chest pain and cough in January 2006. He had a 5-year history of uncontrolled diabetes mellitus. His illness was diagnosed as pneumonia of the left lingular division. Antibiotics were started but his pneumonia worsened repeatedly after insufficient antibiotics due to his poor compliance with medication. In addition to pneumonia, he began to have hemoptysis at the end of May and was admitted to our hospital. Contrast-enhanced CT scan on admission showed a lung abscess on the left lingular division and formation of a pulmonary pseudoaneurysm inside the abscess. Treatment with SBT/ABPC rapidly improved his condition but massive hemoptysis recurred 9 days after admission. Embolization of the bronchial artery and pulmonary pseudoaneurysm successfully controlled airway bleeding. When hemoptysis occurs due to sustained inflammation such as a lung abscess, bleeding from the pulmonary artery should be considered and a precise evaluation including contrast-enhanced CT and pulmonary angiography made.

High expression of Toll-like receptor 4 on CD14+ monocytes in acute infectious diseases.

Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS) and other exogenous and endogenous molecules, and is thought to contribute to defense mechanisms against infections. Our objective was to elucidate the clinical significance of TLR4 in acute infectious diseases by analyzing its sequential expression on CD14+ monocytes. Peripheral blood samples were obtained from 36 patients with acute infectious diseases on admission and after treatment within certain intervals. The TLR4 expression on CD14+ monocytes was analyzed using flow cytometry and was presented as a mean fluorescence intensity (MFI). TLR4 expression during the acute phase of infection was highly enhanced compared to that of normal subjects (MFI: 22.1 vs 8.5). TLR4 expression was promptly reduced to normal levels in parallel with the disease improvement. In patients who died despite treatment, the enhancement of TLR4 expression during the acute phase was less prominent compared to those who survived (MFI: 14.6 vs 23.5) and its sequential change was also subtle. These results indicate that monocytes respond to acute infections by the induction of TLR4 expression and that a poor response may be associated with a poor prognosis.

[A case of visceral larva migrans due to Toxocara canis showing varied manifestations].

A 21-year-old woman admitted for a low-grade fever, dry cough, polyarthralgia, and general fatigue was found to have elevateal accustomed to eating raw meat and cattle liver peripheral blood eosinophil counts and serum IgE. Chest X-ray imaging and computed tomography (CT) showed multiple small nodules in both lung fields. A multiple dot-ELISA assay of her serum showed that she had visceral larva migrans caused by Ascaris suum or Toxocara canis. Following treatment with albendazole, she developed myelopathy and was again admitted. A cerebrospinal fluid examination showed increased eosionophils and significant antibody elevation against T. canis. Her disease was considered to have entered the central nervous system, one of the target organs of visceral larva migrans. She was successfully treated with dietylcarbamazine and has shown no reccurrence. This case showed the different manifestations of visceral larva migrans and the rising incidence of this disease in Japan raises concerns about associated of diet.

Pulmonary infarction as the initial manifestation of Takayasu's arteritis.

A 50-year-old woman reporting sudden-onset chest pain was diagnosed as having pulmonary infarction associated with Takayasus arteritis. She had experienced moderate malaise and cough for 3 months. Computed tomography (CT) and magnetic resonance imaging (MRI) showed wedge-shaped infiltrative shadows typical of pulmonary infarction in the right lung. Although pulmonary artery involvement in Takayasus arteritis is well documented, most patients show only signs of mild to moderate pulmonary hypertension. Few reports discuss patients with symptoms due to pulmonary infarction as the initial manifestation. Takayasus arteritis should therefore be considered a differential diagnosis in pulmonary infarction.