Two cases of systemic capillary leak syndrome associated with COVID-19 in Japan.

Systemic Capillary Leak Syndrome (SCLS) is a rare disease that causes severe distributive shock provoked by infection or vaccination. SCLS is clinically diagnosed by a triad of distributive shock, paradoxical hemoconcentration, and hypoalbuminemia. SCLS associated with coronavirus disease (COVID-19) in adults has not been reported yet in Japan. Case 1: A 61-year-old woman with fever, sore throat, headache, and muscle pain was admitted to our emergency department with suspected COVID-19. She had been diagnosed with SCLS 3 years earlier. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen and polymerase chain reaction (PCR) tests were negative at admission. She went into shock in the emergency department and was treated for septic shock. The following day, the SARS-CoV-2 PCR test was positive. She did not respond to fluid resuscitation and catecholamine and finally died. Case 2: A 58-year-old man was admitted to our hospital for de-saturation due to COVID-19. He got into shock on day 3. SCLS was suspected, and 5 g of intravenous immunoglobulin and 5% albumin were administered for sepsis treatment. He responded to the aggressive fluid therapy within 48 h and was finally discharged. COVID-19 can trigger SCLS, and early recognition of SCLS is crucial for survival. Primary care physicians should consider SCLS when they observe distributive shock and paradoxical hemoconcentration deviations from the natural course of COVID-19.

Non-serogroupable Neisseria meningitidis pneumonia in an immunocompetent patient with severe COVID-19 pneumonia: A case report.

Background: Non-serogroupable Neisseria meningitidis (N. meningitidis), the most common type of N. meningitidis in asymptomatic carriers, rarely causes infections. Most reported cases of infection are in patients with immunodeficiency, primarily complement deficiencies. Case presentation: A 54-year-old immunocompetent man was transferred to our hospital to treat severe coronavirus disease 2019 (COVID-19). The patient presented with cough producing a large amount of purulent sputum, which was considered an atypical presentation of COVID-19. Gram staining of the sputum revealed a large number of gram-negative diplococci phagocytosed by many neutrophils, and a diagnosis of bacterial pneumonia was established. The culture yielded non-serogroupable N. meningitidis, and the patient was diagnosed with non-serogroupable N. meningitidis pneumonia. Potential immunodeficiency was considered; however, testing including human immunodeficiency virus and complement factors showed no abnormalities. Conclusions: We report herein a rare case of non-serogroupable N. meningitidis pneumonia that occurred in an immunocompetent patient during the course of severe COVID-19. We consider impaired T cell function attributable to COVID-19 and dexamethasone administration may have triggered a transient immunosuppressive state and led to non-serogroupable N. meningitidis pneumonia.

Disseminated Toxoplasmosis associated with Haemophagocytic Lymphohistiocytosis in a Patient with the Human Immunodeficiency Virus: A Case Report and Literature Review.

Disseminated toxoplasmosis associated with haemophagocytic lymphohistiocytosis (DT-HLH) is rare and difficult to diagnose compared to disseminated toxoplasmosis or HLH presenting alone. Because of the limited number of reported cases, the clinical characteristics and outcomes of DT-HLH are unknown. We report a case of DT-HLH in a human immunodeficiency virus (HIV)-infected patient who was successfully treated with early anti-toxoplasmic therapy and performed a comprehensive literature review. A 33-year-old Cameroonian woman was transferred to our hospital owing to HIV infection and encephalitis. Although she developed HLH, bone marrow biopsy did not reveal the cause. She was diagnosed as having DT-HLH via polymerase chain reaction testing of bone marrow biopsy tissue, blood, and cerebrospinal fluid. DT-HLH improved within the initial two weeks of treatment for toxoplasmosis (sulfamethoxazole-trimethoprim, trimethoprim 10 mg/kg/day and clindamycin 1,800 mg/day) before the introduction of antiretroviral therapy. To our knowledge, only eight cases of DT-HLH have been previously reported in the literature. Most patients died within three weeks of hospitalisation and were diagnosed by autopsy. Conversely, patients diagnosed antemortem were all treated and survived, including the currently reported patient. DT-HLH can lead to poor prognosis without early and proper treatment. Clinicians should consider toxoplasmosis in the differential diagnosis of HLH.

Nosocomial outbreak of coronavirus disease in two general wards during the initial wave of the pandemic in 2020, Tokyo, Japan.

Objective: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in China and subsequently spread worldwide. In Japan, many clusters occurred during the first wave in 2020. We describe the investigation of an early outbreak in a Tokyo hospital. Methods: A COVID-19 outbreak occurred in two wards of the hospital from April to early May 2020. Confirmed cases were individuals with laboratory-confirmed SARS-CoV-2 infection linked to Wards A and B, and contacts were patients or workers in Wards A or B 2 weeks before the index cases developed symptoms. All contacts were tested, and cases were interviewed to determine the likely route of infection and inform the development of countermeasures to curb transmission. Results: There were 518 contacts, comprising 472 health-care workers (HCWs) and 46 patients, of whom 517 were tested. SARS-CoV-2 infection was confirmed in 42 individuals (30 HCWs and 12 patients). The proportions of SARS-CoV-2 infections in HCWs were highest among surgeons, nurses, nursing assistants and medical assistants. Several HCWs in these groups reported being in close proximity to one another while not wearing medical masks. Among HCWs, infection was thought to be associated with the use of a small break room and conference room. Discussion: Nosocomial SARS-CoV-2 infections occurred in two wards of a Tokyo hospital, affecting HCWs and patients. Not wearing masks was considered a key risk factor for infection during this outbreak; masks are now a mandated countermeasure to prevent the spread of SARS-CoV-2 infection in hospital settings.

COVID-19-associated leukoencephalopathy in the absence of severe hypoxia with subsequent improvement: a case report.

BACKGROUND: Several cases of coronavirus disease 2019 (COVID-19)-associated leukoencephalopathy have been reported. Although most cases involve hypoxia, the pathophysiological mechanism and neurologic outcomes of COVID-19-associated leukoencephalopathy remain unclear. CASE PRESENTATION: We report a case of COVID-19-associated leukoencephalopathy without severe hypoxia in a 65-year-old woman diagnosed with pyelonephritis. After the initiation of intravenous ceftriaxone, her fever resolved, but she developed an altered state of consciousness with abnormal behavior and, subsequently, a relapse fever. She was diagnosed with COVID-19 pneumonia and was intubated. Lung-protective ventilation with deep sedation and neuromuscular blockade were used for treatment. After cessation of sedative administration, her mental status remained at a Glasgow Coma Scale score of 3. COVID-19 was assumed to have caused leukoencephalopathy due to the absence of severe hypoxia or other potential causes. She subsequently showed gradual neurologic improvement. Three months after the COVID-19 diagnosis, she regained alertness, with a Glasgow Coma Scale score of 15. CONCLUSION: Clinicians should consider leukoencephalopathy in the differential diagnosis of consciousness disorders in patients with severe COVID-19, even in the absence of severe hypoxia. Gradual neurologic improvement can be expected in such cases.

Current antimicrobial prescription at outpatient dentistry centers and clinics in tertiary-care hospitals in Tokyo, Japan: A multicenter cross-sectional study.

Background: Antimicrobial administration is necessary before specific dental procedures to prevent postprocedural infections and complications and antimicrobials are sometimes indicated for the treatment of odontogenic infections. However, antimicrobials are commonly misused by dentists. Methods: This cross-sectional study was conducted at 4 public, tertiary-care hospitals in Tokyo, Japan, from June to July 2019. We included patients who received an antimicrobial prescription at the outpatient dentistry center or clinic at each participating hospital. The indications for antimicrobial prescription were (1) antimicrobial prescriptions for prophylaxis (APPs) or (2) antimicrobial prescriptions for treatment (APTs). Prescribing patterns were described in terms of antimicrobial choice, timing, and dosages for APPs and APTs. Results: During the study period, 1,772 patients received an antimicrobial prescription. Among them 1,439 (81.2%) were APPs and 333 (18.8%) were APTs. The most common aim of APP was to prevent local infections and complications following tooth extraction (n = 1,244, 86.4%). The proportion of appropriate APPs was only 0.8% (12 of 1,439). Among 1,439 total APPs, 171 (11.9%) were unnecessary, 32 (2.2%) were inappropriate, and 1,224 (85.1%) were suboptimal. Whereas 101 (30.3%) of 333 APTs were appropriate, the remaining 97 instances (29.1%) were unnecessary, 86 (26.7%) were inappropriate, and 46 (13.8%) were suboptimal. Conclusion: Inappropriate antimicrobial prescriptions were common among dentists in Japan. Understanding the differences in the current antimicrobial prescribing patterns for prophylaxis and treatment is critically important for implementing an effective antimicrobial stewardship program in dentistry.

Critically ill patients with COVID-19 in Tokyo, Japan: A single-center case series.

INTRODUCTION: We reported, in our previous study, a patient with coronavirus disease 2019 (COVID-19) who was successfully treated with extracorporeal membrane oxygenation. Data on clinical courses and outcomes of critically ill patients with COVID-19 in Japan are limited in the literature. This study aimed to describe the clinical courses and outcomes of critically ill patients with COVID-19 in Tokyo, Japan. METHODS: This is a single-center case series study. Patients with COVID-19 treated with mechanical ventilation (MV) were reviewed retrospectively. Data on baseline characteristics, in-hospital treatment, and outcomes were collected. RESULTS: Between February 2, 2020, and June 30, 2020, 14 critically ill patients with COVID-19 were treated with MV. Most patients were male and had comorbidities, especially hypertension or diabetes; 35.7% were overweight and 21.4% were obese. The majority of the patients had dyspnea on admission. The median duration of MV was 10.5 days, and the 28-day mortality rate was 35.7%. In the four patients with COVID-19 who died, the cause of death was respiratory failure. CONCLUSIONS: As in previous reports from other countries, the mortality rate of patients with COVID-19 requiring intensive care remains high in Tokyo. Further study on the appropriate timing of MV initiation and specific treatments for critically ill patients with COVID-19 is needed.

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.

Failure of Liposomal-amphotericin B Treatment for New World Cutaneous Leishmaniasis due to Leishmania braziliensis.

Liposomal-amphotericin B (L-AmB) is used for cutaneous leishmaniasis (CL); however, its treatment failure has not yet been described in detail. A 58-year-old man returned from the Republic of Venezuela with a cutaneous ulcer on his left lower leg. The causative pathogen was Leishmania braziliensis. We started L-AmB 3 mg/kg/day for 6 days; however, the ulcer did not resolve. The patient was successfully retreated with a higher dose L-AmB 4 mg/kg/day 9 times (total, 36 mg/kg). If L-AmB fails to treat CL and other therapeutics cannot be used, increasing the L-AmB dose is a viable option.

Pre-transfusion testing for Ebola virus disease patients in serious communicable infectious diseases hospitals in Tokyo: A cross-sectional study.

BACKGROUND: Ebola virus disease (EVD) was endemic to Africa in 2014-2016. Supportive therapies have been shown to improve the outcome of EVD, and additional supportive therapy including blood transfusion therapy and external circulation could be needed in the event of a future global outbreak. However, pre-transfusion testing policies and guidelines have not yet been established in Japan. METHODS: We conducted a cross-sectional study of blood transfusion therapy for EVD patients at three designated hospitals for serious communicable diseases in Tokyo. In each hospital, we surveyed blood transfusion therapy policy, blood transfusion protocol, presence of a specialist in the department of transfusion medicine, facility capacity for pre-transfusion compatibility testing, and types of personal protective equipment available. RESULTS: One hospital had a cross-matched compatible blood transfusion policy, one had a cross-matched compatible blood transfusion policy only when the patient's ABO and RhD type is previously known, and the third had not created a policy. Two hospitals had a department of transfusion medicine. These two hospitals had a special testing unit for serious communicable diseases, while the other had a portable unit for testing. There were no major differences noted in available personal protective equipment. CONCLUSION: Policies and protocols differ among hospitals. The choice of blood transfusion policy and pre-transfusion testing is largely dependent on equipment and human resources. Further discussion is required to develop national guidelines for blood transfusion therapy in patients with serious communicable diseases, including countermeasures against complications and ethical issues related to the safety of patients and healthcare workers.

Non-invasive diagnosis of cutaneous leishmaniasis by the direct boil loop-mediated isothermal amplification method and MinION™ nanopore sequencing.

Cutaneous leishmaniasis (CL) is gaining attention as a public health problem. We present two cases of CL imported from Syria and Venezuela in Japan. We diagnosed them as CL non-invasively by the direct boil loop-mediated isothermal amplification method and an innovative sequencing method using the MinION™ sequencer. This report demonstrates that our procedure could be useful for the diagnosis of CL in both clinical and epidemiological settings.