Field-deployable multiplex detection method of SARS-CoV-2 and influenza virus using loop-mediated isothermal amplification and DNA chromatography.

A novel multiplex loop-mediated isothermal amplification (LAMP) method combined with DNA chromatography was developed for the simultaneous detection of three important respiratory disease-causing viruses: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, and influenza B virus. Amplification was performed at a constant temperature, and a positive result was confirmed by a visible colored band. An in-house drying protocol with trehalose was used to prepare the dried format multiplex LAMP test. Using this dried multiplex LAMP test, the analytical sensitivity was determined to be 100 copies for each viral target and 100-1000 copies for the simultaneous detection of mixed targets. The multiplex LAMP system was validated using clinical COVID-19 specimens and compared with the real-time qRT-PCR method as a reference test. The determined sensitivity of the multiplex LAMP system for SARS-CoV-2 was 71% (95% CI: 0.62-0.79) for cycle threshold (Ct) ≤ 35 samples and 61% (95% CI: 0.53-0.69) for Ct ≤40 samples. The specificity was 99% (95%CI: 0.92-1.00) for Ct ≤35 samples and 100% (95%CI: 0.92-1.00) for the Ct ≤40 samples. The developed simple, rapid, low-cost, and laboratory-free multiplex LAMP system for the two major important respiratory viral diseases, COVID-19 and influenza, is a promising field-deployable diagnosis tool for the possible future 'twindemic, ' especially in resource-limited settings.

Epidemiological trends of traveler's diarrhea in Japan: An analysis of imported infectious disease registry data from 2017-2022.

Traveler's diarrhea (TD) is a global problem, and identifying the causative organisms of TD is important for adequate treatment. Therefore, this study retrospectively analyzed TD cases in patients who returned to Japan after traveling abroad to determine the causative organisms by travel region. We included patients with a final diagnosis of TD registered in the Japan Registry for Infectious Diseases from Abroad database from September 25, 2017, to September 1, 2022, from 14 medical institutions. A total of 919 patients were analyzed; the causative TD pathogen was identified in 188 cases (20%), of which 154 were caused by diarrheagenic bacteria, the most common being Campylobacter spp. (64%). A 2.2 mg/dL C-reactive protein concentration cutoff value had some predictive ability for bacterial TD (negative predictive value, 89%). Therefore, the C-reactive protein level may help rule out bacterial diarrhea and prevent unnecessary antimicrobial administration when patients cannot provide a stool specimen.

Successful immunomodulation in kidney transplant recipients with cytokine release syndrome after coronavirus disease.

Introduction: Patients with coronavirus disease, especially solid organ transplant recipients, are more susceptible to developing cytokine release syndrome than those with other viral infections. However, currently, treatment methods for such patients have not been established. Here, we describe two cases of successful immunomodulation in Japanese kidney transplant recipients with cytokine release syndrome following coronavirus disease. Case presentation: Two patients who had been receiving long-term immunosuppressant therapy developed coronavirus disease-associated pneumonia caused by cytokine release syndrome, following immunosuppressant dosage reduction. However, they recovered immediately after administration of tocilizumab with or without dexamethasone. Conclusion: The immunosuppressant dosage should be reduced to restore host immunity; however, immunomodulation should be considered in cases of suspected cytokine release syndrome.

A novel nairovirus associated with acute febrile illness in Hokkaido, Japan.

The increasing burden of tick-borne orthonairovirus infections, such as Crimean-Congo hemorrhagic fever, is becoming a global concern for public health. In the present study, we identify a novel orthonairovirus, designated Yezo virus (YEZV), from two patients showing acute febrile illness with thrombocytopenia and leukopenia after tick bite in Hokkaido, Japan, in 2019 and 2020, respectively. YEZV is phylogenetically grouped with Sulina virus detected in Ixodes ricinus ticks in Romania. YEZV infection has been confirmed in seven patients from 2014-2020, four of whom were co-infected with Borrelia spp. Antibodies to YEZV are found in wild deer and raccoons, and YEZV RNAs have been detected in ticks from Hokkaido. In this work, we demonstrate that YEZV is highly likely to be the causative pathogen of febrile illness, representing the first report of an endemic infection associated with an orthonairovirus potentially transmitted by ticks in Japan.

Immediate Amelioration of Severe Respiratory Distress in Sjögren's Syndrome with COVID-19 Treated with a Single Dose of Off-label Tocilizumab.

The coronavirus disease 2019 (COVID-19) pandemic has become an urgent global health issue. An older age and underlying conditions, such as diabetes, have been reported as risk factors, but whether or not autoimmune diseases increase the risk remains unknown. An 85-year-old man with Sjögren's syndrome developed a severe COVID-19 infection that required oxygen supplementation. After discussing the goals of care with him and his wife, off-label tocilizumab was given concomitantly, resulting in a rapid improvement in his symptoms and respiratory failure. This patient represents a supplementary case confirming the efficacy and safety of tocilizumab for COVID-19 in elderly patients with autoimmune diseases.

Epidemiological trends of imported infectious diseases in Japan: Analysis of imported 2-year infectious disease registry data.

INTRODUCTION: The epidemiology of infectious diseases in Japan remains undefined despite the increasing tourism. GeoSentinel, an epidemiological surveillance system for reporting imported infectious diseases, has only two participating facilities in Japan. Although the number of infectious diseases is reported by the National Institute of Infectious Diseases, there is no detailed clinical information about these cases. Therefore, we established J-RIDA (Japan Registry for Infectious Diseases from Abroad) to clarify the status of imported infectious diseases in Japan and provide detailed information. METHODS: J-RIDA was started as a registry of imported infectious diseases. Case registration began in October 2017. Between October 2017 and September 2019, 15 medical institutions participated in this clinical study. The registry collected information about the patient's age, sex, nationality, chief complaint, consultation date, date of onset, whether visit was made to a travel clinic before travel, blood test results (if samples were collected), travel history, and final diagnosis. RESULTS: Of the 3046 cases included in this study, 46.7% to Southeast Asia, 13.0% to Africa, 13.7% to East Asia, 11.5% to South Asia, 7.5% to Europe, 3.8% to Central and South America, 4.6% to North America, 3.9% to Oceania, and 2.8% to Central and west Asia. More than 85% of chief complaints were fever and general symptoms, gastrointestinal symptoms, respiratory symptoms, or dermatologic problems. The most common diseases were travelers' diarrhea, animal bite, upper respiratory infection, influenza, and dengue fever. CONCLUSIONS: We summarized two-year cases registered in Japan's imported infectious disease registry. These results will significantly contribute to the epidemiology in Japan.

Epidemiological features after emergency declaration in Hokkaido and report of 15 cases of COVID-19 including 3 cases requiring mechanical ventilation.

The ongoing spread of coronavirus disease (COVID-19) is a worldwide crisis. Hokkaido Prefecture in Japan promptly declared a state of emergency following the rapid increase of COVID-19 cases, and the policy became an example to mitigate the spread of COVID-19. We herein report 15 cases of COVID-19 including 3 cases requiring mechanical ventilation. Based on review of our cases, among patients over 50 years of age with underlying diseases such as hypertension and diabetes mellitus, and those who required oxygen administration tended to deteriorate. These cases highlight the importance of understanding the background and clinical course of severe cases to predict prognosis.

Early surgery with aggressive surgical approach to improve 6-month outcomes in patients with active infective endocarditis: contribution of cerebral preoperative magnetic resonance imaging.

OBJECTIVES: We investigated the hypothesis that early surgery for infective endocarditis (IE) attenuates the rate of death or embolic events and does not increase the rate of relapse or postoperative valvular dysfunction (PVD) at 6 months. METHODS: 21 consecutive patients who underwent surgical treatment of IE were prospectively included. We assessed 6-month postoperative clinical outcomes by comparing early surgery (Group E, surgery within 72 h) and conventional treatment (Group C). Nine patients (43%) were assigned to Group E based on a combination of preoperative evaluation parameters, including the findings of cerebral magnetic resonance imaging (MRI), which was performed in all patients with left-sided IE. RESULTS: Six surgical plans (5 advancements and 1 postponement) were modified by routine MRI. Although preoperative echocardiography did not confirm all annular invasions, the rate of periannular infection, which was treated by pericardial annular patch plasty (56%) in patients with native-valve IE, was higher in Group E than C (P = 0.006). Early surgery based on MRI findings resulted in no postoperative embolic events or cerebral bleeding. The 6-month mortality rate was 0% in both groups, although the calculated 6-month IE mortality rate was 49.2 ± 25% and 28.8 ± 18%, respectively. No recurrence of IE or PVD occurred in Group E. The 6-month rate of freedom from composite events was 100% in Group E. CONCLUSIONS: Aggressive treatment (periannular resection and disuse of a prosthetic annuloplasty ring) and optimal antibiotic therapy based on intraoperative microorganisms, even in patients who underwent early surgery, reduced the 6-month relapse and PVD rates.

Acute kidney injury caused by systemic Neisseria gonorrhoeae infection after successful kidney transplantation.

Neisseria gonorrhoeae is one of the microbes that can causes male urethritis. This microbe is most likely to be transmitted via sexual intercourse. In men, the representative infection sites are the urethra, and oral mucosa but gonococcemia is rere. We present a case of gonococcemia in a 47-year-old male successful kidney recipient. He temporarily lost his graft function due to acute kidney injury followed by sepsis; however, short-course intermittent hemodialysis and long-term intensive ceftriaxone inoculation saved his life and his graft function.

Respiratory Syncytial Virus and Other Noninfluenza Respiratory Viruses in Older Adults.

Respiratory viral infections may cause serious complications for older adults, including residents of long-term care facilities (LTCFs). Although influenza is the most common cause of viral respiratory infections among older adults, several other respiratory viruses also cause significant morbidity and mortality, most notably respiratory syncytial virus. Other noninfluenza respiratory viral pathogens include human metapneumovirus, parainfluenza virus, rhinovirus, coronavirus, and adenovirus. All of these may cause outbreaks among LTCF residents. Recently developed rapid diagnostic molecular tests may clarify the epidemiology of these viruses and have potential, through early identification, to limit the severity of outbreaks among older adults living in LTCFs.

[Clinical Characteristics of Invasive Pneumococcal Disease of the Mucoid Phenotype: A Case Series].

Streptococcus pneumoniae is a gram-positive coccus that causes invasive and non-invasive pneumococcal diseases. Invasive pneumococcal disease (IPD) is defined as an infection confirmed by the isolation of S. pneumoniae from a normally sterile site. IPD has a high mortality rate of around 20% in adults. Colonies of S. pneumoniae show various morphological features which include a mucoid appearance. The production of large amounts of capsular polysaccharide gives colonies of S. pneumoniae their mucoid appearance. This is thought to be a mechanism of microbial escape from phagocyte killing, leading to strong pathogenicity despite their high susceptibility to antibiotics. To our knowledge, the clinical characteristics of patients with mucoid IPD are unknown. We retrospectively analyzed the records of adult patients with IPD of the mucoid phenotype at Teine Keijinkai Hospital, Hokkaido, Japan, between 2009 and 2015. Seven patients (six males) with age range between 62 and 80 years were diagnosed as having mucoid IPD during the study period. Two patients had a history of malignancy and diabetes mellitus respectively, and six patients were living independently. No patients were previously vaccinated with pneumococcal vaccine. Six patients had clinical manifestations of pneumonia; one patient had multiple concomitant complications of mastoiditis, meningitis, and prosthetic joint infection. All isolates were isolated from blood. All isolates were susceptible to beta-lactam antibiotics, while six isolates were resistant to macrolides and chloramphenicol. Based on the Quellung reaction and real-time polymerase chain reaction (PCR) results, one isolate of mucoid phenotype was confirmed as serotype 3 with the penicillin binding protein gene of pbp2x and the macrolide resistant gene of ermB. Although all patients received appropriate antibiotics based on susceptibility testing, four patients required mechanical ventilation and vasopressors. One patient had neurological sequelae (hypacusis) and two patients died during the course of hospitalization. This case series suggests that mucoid IPD can occur in immunocompetent hosts and can cause high mortality. Since most of the mucoid phenotype of S. pneumoniae are serotype 3, widespread use of pneumococcal vaccine is important to prevent morbidity and mortality associated with IPD.