The effect of infectious diseases on lung transplantation in Japan.

Lung transplantation in Japan is an increasingly accessible treatment option for end-stage lung disease; however, the lack of donor organs is a persisting challenge. Five- and 10-year survival rates of lung transplant recipients in Japan are comparable, if not superior, to international standards. The outcomes of lung transplantation in Japan are likely affected by multiple factors. Infectious disease complications are a significant burden to transplant recipients and account for approximately 30% of recipient mortality in Japan, presenting a major challenge in peri-transplant management. Herein, we explore the current status of infectious disease epidemiology, available evidence surrounding infectious diseases in lung transplantation, and potentially influential factors pertinent to lung transplantation outcomes in Japan. Although infection remains the major cause of morbidity and mortality associated with lung transplantation in Japan, there is limited data and evidence. Despite some uncertainties, publicly available data suggests a low rate of antimicrobial resistance in Gram-negative bacteria and a distinct set of endemic pathogens that recipients may encounter. As a countermeasure against the burden of infectious diseases, 8 out of 10 transplant centers in Japan have a dedicated infectious diseases department. Despite these efforts, specific surveillance, prevention, and management are indispensable to improving post-transplantation infectious disease management. We accordingly lay out potential areas for improving infectious disease-related outcomes among lung transplant recipients in Japan.

Evaluation of a novel severe combined immunodeficiency mouse model for antiviral drug evaluation against Chandipura virus infection.

Chandipura virus (CHPV) is a negative-sense single-stranded RNA virus known to cause fatal encephalitis outbreaks in the Indian subcontinent. The virus displays tropism towards the pediatric population and holds significant public health concerns. Currently, there is no specific, effective therapy for CHPV encephalitis. In this study, we evaluated a novel C.B-17 severe combined immunodeficiency (SCID) mouse model which can be used for pre-clinical antiviral evaluation. Inoculation of CHPV developed a lethal infection in our model. Plaque assay and immunohistochemistry detected increased viral loads and antigens in various organs, including the brain, spinal cord, adrenal glands, and whole blood. We further conducted a proof-of-concept evaluation of favipiravir in the SCID mouse model. Favipiravir treatment improved survival with pre-symptomatic (days 5-14) and post-symptomatic (days 9-18) treatment. Reduced viral loads were observed in whole blood, kidney/adrenal gland, and brain tissue with favipiravir treatment. The findings in this study demonstrate the utility of SCID mouse for in vivo drug efficacy evaluation and the potential efficacy of favipiravir against CHPV infection.

Japan perspective on antimicrobial stewardship and solid organ transplantation.

BACKGROUND: The current situation, challenges, and opportunities related to antimicrobial stewardship for solid organ transplantations (SOTs) patients in Japan are not well known. METHODS: We searched English and Japanese literature using Pubmed and Ichushi-Web (the Japanese medical literature search system provided by the Japan Medical Abstract Society) with relevant keywords including solid organ transplant, antimicrobial stewardship, and Japan. Hand searches of the references from the retrieved literature, including conference proceedings of The Japanese Association for Infectious Diseases, were conducted. RESULTS: The Japanese National Action Plan for antimicrobial resistance has brought attention to the importance of antimicrobial stewardship programs (ASPs) in Japan. According to national surveillance, the proportion of methicillin resistance among Staphylococcus aureus was 48%, while the proportion of vancomycin-resistance among Enterococcus faecium was 1.5% in 2019. Resistance against imipenem in Escherichia coli and Klebsiella pneumoniae in 2019 were 0.1% and 0.2%, respectively. Exploration of SOT-specific data on antimicrobial usage and drug resistance are warranted. A large questionnaire survey revealed a low proportion of hospitals with >500 beds implementing ASP toward immunocompromised patients. While the annual number of SOT in Japan has increased, the implementation of SOT-specific ASP varies among institutions. CONCLUSION: A coordinated ASP and exploration of the burden of antimicrobial resistance are needed for SOT patients in Japan. Promoting both intrainstitutional and interinstitutional collaboration is vital to the advancement of SOT-specific ASP in Japan.

A Cold-Blooded Tiptoer: Nonresolving Cellulitis in an Immunocompromised Patient.

Mycobacterium haemophilum is a nontuberculous mycobacteria (NTM) with a predilection for skin and soft tissue infection (SSTI) in the immunocompromised host. We report a case of disseminated M haemophilum infection initially presenting as a nonresolving subacute cellulitis of bilateral lower extremities. Genetic sequencing was used for final identification, while a commercially available polymerase chain reaction test returned a false-positive result for Mycobacterium intracellulare. Consequently, we highlight the importance of M haemophilum as a major differential diagnosis of SSTI in the immunocompromised host and the need for careful interpretation of rapid diagnostic tests.

First human case of catheter-related blood stream infection caused by Staphylococcus schleiferi subspecies coagulans: a case report and literature review.

BACKGROUND: Staphylococcus schleiferi is a gram-positive pathogenic coccus which causes canine skin and ear infections. Only four cases of human infection caused by Staphylococcus schleiferi subspecies coagulans have been reported. Herein, we present the first case of catheter-related bloodstream infection caused by S. schleiferi subspecies coagulans. CASE PRESENTATION: A 62-year-old Japanese man was admitted to our hospital for examination of sigmoid colon tumor. During hospitalization, he had fever, shaking chills, and swelling at the peripheral venous catheter insertion site. Two sets of blood cultures were positive for S. schleiferi subspecies coagulans which was confirmed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), 16S ribosomal RNA sequencing and the coagulase test. The patient was successfully treated without relapse. CONCLUSION: To our knowledge, this is the first report of catheter-related bloodstream infection caused by S. schleiferi subspecies coagulans. S. schleiferi subsp. coagulans can be pathogenic in humans, and MALDI-TOF MS can contribute to accurate identification of S. schleiferi subspecies coagulans.

Favipiravir treatment prolongs the survival in a lethal mouse model intracerebrally inoculated with Jamestown Canyon virus.

BACKGROUND: Jamestown Canyon virus (JCV) is a mosquito-borne orthobunyavirus that causes acute febrile illness, meningitis, and meningoencephalitis, primarily in North American adults. Currently, there are no available vaccines or specific treatments against JCV infections. METHODOLOGY/PRINCIPAL FINDINGS: The antiviral efficacy of favipiravir (FPV) against JCV infection was evaluated in vitro and in vivo in comparison with that of ribavirin (RBV) and 2'-fluoro-2'-deoxycytidine (2'-FdC). The in vitro inhibitory effect of these drugs on JCV replication was evaluated in Vero and Neuro-2a (N2A) cells. The efficacy of FPV in the treatment of JCV infection in vivo was evaluated in C57BL/6J mice inoculated intracerebrally with JCV, as per the survival, viral titers in the brain, and viral RNA load in the blood. The 90% inhibitory concentrations (IC90) of FPV, RBV, and 2'-FdC were 41.0, 61.8, and 13.6 µM in Vero cells and 20.7, 25.8, and 8.8 µM in N2A cells, respectively. All mice infected with 1.0×104 TCID50 died or were sacrificed within 10 days post-infection (dpi) without treatment. However, mice treated with FPV for 5 days [initiated either 2 days prior to infection (-2 dpi-2 dpi) or on the day of infection (0 dpi-4 dpi)] survived significantly longer than control mice, administered with PBS (p = 0.025 and 0.011, respectively). Moreover, at 1 and 3 dpi, the virus titers in the brain were significantly lower in FPV-treated mice (0 dpi-4 dpi) versus PBS-treated mice (p = 0.002 for both 1 and 3 dpi). CONCLUSIONS/SIGNIFICANCE: Although the intracerebral inoculation route is thought to be a challenging way to evaluate drug efficacy, FPV inhibits the in vitro replication of JCV and prolongs the survival of mice intracerebrally inoculated with JCV. These results will enable the development of a specific antiviral treatment against JCV infections and establishment of an effective animal model.

Development of an assay for detecting the residual viable virus in inactivated rabies vaccine by enzyme-linked immunosorbent assay.

Rabies is a zoonotic disease that can be prevented by vaccination. The confirmation of rabies virus inactivation is a critical step during the vaccine quality test; however, the current protocol conducted in Japan requires a large number of mice. The development and introduction of animal-free alternative assays are essential from the perspective of the 3Rs (reduction, refinement, and replacement) of animal testing. Here, we propose a novel inactivation assay for confirming the complete inactivation of the viable rabies virus using cultured Neuro-2a cells and an enzyme-linked immunosorbent assay (ELISA). The detection ability of ELISA was similar to that of a direct immunofluorescence assay, with the detection limit of ELISA being as low as 0.014 focus forming units/test. These results suggest that the assay could be used as a viral inactivation test. In comparison with a traditional in vivo assay, this assay has a higher detection ability, an objective interpretation, and would shorten the test duration from 25 days to 8 days.

First Reported Human Case of Spondylodiscitis by Staphylococcus condimenti: A Case Report and Literature Review.

Staphylococcus condimenti is a Gram-positive coccus that was first isolated from soy sauce mash. Only four cases of human S. condimenti infections have been reported to date. We herein report the first case of spondylodiscitis caused by S. condimenti. A 72-year-old Japanese man complaining of lower back pain and numbness in his legs was diagnosed with spondylodiscitis. A computed tomography (CT)-guided biopsy was performed. A culture of the intravertebral disc aspirate yielded S. condimenti. The result was confirmed using gene sequencing methods. The patient was successfully treated without relapse. This case shows that S. condimenti can be pathogenic and cause invasive infection.

Seroprevalence of Jamestown Canyon virus in the Japanese general population.

BACKGROUND: Jamestown Canyon virus (JCV) is a mosquito-borne orthobunyavirus that causes acute febrile illness, meningitis, and meningoencephalitis, mainly among adults. JCV is widely distributed in North America and the number of JCV cases in the U.S. has increased in recent years. Therefore, the central nervous system disease caused by JCV can be considered a potentially re-emerging viral disease. However, the seroprevalence of JCV is unknown in Japan. The purpose of this study is to evaluate the seroprevalence of JCV in the Japanese population. METHODS: We used an IgG enzyme-linked immunosorbent assay (IgG-ELISA) with JCV-infected cell-lysates and/or a neutralizing (NT) antibody assay. The cut-off value of IgG-ELISA was determined using IgG-ELISA to analyze serum specimens from 37 healthy Japanese donors. IgG-ELISA was validated by assessing its sensitivity and specificity, using 38 human serum samples previously tested for the presence or absence of antibodies against JCV and snowshoe hare virus (SSHV), in an in-house NT antibody assay conducted by the Public Health Agency of Canada. The seroepidemiological study was performed using IgG-ELISA and NT antibody assay to analyze 246 human serum samples from the serum bank of the National Institute of Infectious Diseases (NIID) in Japan. RESULTS: The cut-off value of IgG-ELISA was determined at 0.20, based on the mean (- 0.075) and standard deviation (0.092) values using Japanese donors' sera. The sensitivity and the specificity of IgG-ELISA determined using 25 JCV-positive and 4 JCV-negative serum samples were 96 and 100%, respectively. Analysis of the 246 Japanese serum samples revealed that no specimen showed a higher value than the cut-off value of IgG-ELISA, and no sample tested positive by the NT antibody assay. CONCLUSIONS: Our results showed that JCV is not circulating significantly in Japan. To the best of our knowledge, this is the first report to demonstrate the seroprevalence of JCV in the general population in Japan.

Vibrio fluvialis Liver Abscess and Bacteremia in a Sashimi Lover: A Case Report and Review of the Literature.

Vibrio fluvialis is a foodborne pathogen known to cause a cholera-like gastroenteritis syndrome. Here we report the first case of V. fluvialis liver abscess and bacteremia presumed to be from sashimi, a Japanese raw seafood delicacy. We also provide a literature review of reported cases of V. fluvialis extra-intestinal diseases including bacteremia.

The First Case Report of Acute Symptomatic HEV Genotype 4 Infection in an HIV-positive Patient in Japan.

Hepatitis E virus (HEV) is a common cause of acute hepatitis. Four major genotypes of HEV have been studied, with genotype 4 being the predominant genotype across Asia. We herein describe the case of a 50-year-old man with a history of human immunodeficiency virus (HIV) infection who was admitted with acute transaminitis. Serum anti-HEV-IgA and HEV-RNA were detected at the time of presentation and further testing revealed HEV genotype 4. To the best of our knowledge, this represents the first clinical case report of acute symptomatic HEV genotype 4 infection in an HIV-positive patient in Japan.

Bacterial peritonitis in a patient with malignant ascites caused by pancreatic carcinoma: Case report and review of literature.

Bacterial peritonitis, an infection of the ascitic fluid, can be classified etiologically as spontaneous or secondary bacterial peritonitis. The former is mainly caused by portal hypertension and its subsequent effects, whereas the latter is caused by the direct dissemination of bacteria into the peritoneal cavity. Previous reports have described some distinguishing features of these two entities. Here, we report the first known case of bacterial peritonitis with Aeromonas hydrophilia and Escherichia coli in a patient with malignant ascites associated with pancreatic carcinoma who exhibited features of both spontaneous and secondary peritonitis. Our report suggests that clinicians should also consider bacterial peritonitis in patients with malignant ascites who present with ostensibly cancer-related symptoms.