Abnormally High Levels of Virus-Infected IFN-γ+CCR4+CD4+CD25+ T Cells in a Retrovirus-Associated Neuroinflammatory Disorder

BACKGROUND:Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus associated with both HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic neuroinflammatory disease, and adult T-cell leukemia (ATL). The pathogenesis of HAM/TSP is known to be as follows: HTLV-1-infected T cells trigger a hyperimmune response leading to neuroinflammation. However, the HTLV-1-infected T cell subset that plays a major role in the accelerated immune response has not yet been identified. PRINCIPAL FINDINGS:Here, we demonstrate that CD4(+)CD25(+)CCR4(+) T cells are the predominant viral reservoir, and their levels are increased in HAM/TSP patients. While CCR4 is known to be selectively expressed on T helper type 2 (Th2), Th17, and regulatory T (Treg) cells in healthy individuals, we demonstrate that IFN-gamma production is extraordinarily increased and IL-4, IL-10, IL-17, and Foxp3 expression is decreased in the CD4(+)CD25(+)CCR4(+) T cells of HAM/TSP patients as compared to those in healthy individuals, and the alteration in function is specific to this cell subtype. Notably, the frequency of IFN-gamma-producing CD4(+)CD25(+)CCR4(+)Foxp3(-) T cells is dramatically increased in HAM/TSP patients, and this was found to be correlated with disease activity and severity. CONCLUSIONS:We have defined a unique T cell subset--IFN-gamma(+)CCR4(+)CD4(+)CD25(+) T cells--that is abnormally increased and functionally altered in this retrovirus-associated inflammatory disorder of the central nervous system

First nationwide survey of infection prevention and control among healthcare facilities in japan : impact of the national regulatory system

Background: Infection prevention and control (IPC) measures in Japan are facilitated by a financial incentive process at the national level, where facilities are categorized into three groups (Tier 1, Tier 2, or no financial incentive). However, its impact on IPC at the facility level using a validated tool has not been measured. Methods: A nationwide cross-sectional study was conducted from August 2019 to January 2020 to evaluate the situation of IPC programs in Japan, using the global IPC Assessment Framework (IPCAF) developed by the World Health Organization. Combined with the information on the national financial incentive system, the demographics of facilities and each IPCAF item were descriptively analyzed. IPCAF scores were analyzed according to the facility level of care and the national financial incentive system for IPC facility status, using Dunn-Bonferroni and Mann-Whitney U tests. Results: Fifty-nine facilities in Japan responded to the IPCAF survey: 34 private facilities (57.6%) and 25 public facilities (42.4%). Of these, 11 (18.6%), 29 (49.2%), and 19 (32.3%) were primary, secondary, and tertiary care facilities, respectively. According to the national financial incentive system for IPC, 45 (76.3%), 11 (18.6%), and three (5.1%) facilities were categorized as Tier 1, Tier 2, and no financial incentive system, respectively. Based on the IPCAF total score, more than half of the facilities were categorized as "Advanced" (n = 31, 55.3%), followed by "Intermediate" (n = 21, 37.5%). The IPCAF total score increased as the facility level of care increased, while no statistically significant difference was identified between the secondary and tertiary care facilities (p = 0.79). There was a significant difference between Tier 1 and Tier 2 for all core components and total scores. Core components 5 (multimodal strategies for implementation of IPC interventions) and 6 (monitoring/audit of IPC and feedback) were characteristically low in Japan with a median score of 65.0 (interquartile range 40.0-85.0) and 67.5 (interquartile range 52.5-87.5), respectively. Conclusions: The national financial incentive system was associated with IPC programs at facility level in Japan. The current financial incentive system does not emphasize the multimodal strategy or cover monitoring/audit, and an additional systematic approach may be required to further promote IPC for more practical healthcare-associated infection prevention.</p

Surveillance and risk assessment of health screening for vaccine-preventable diseases among international students in Japan: A cross-sectional study in 2020

We conducted a cross-sectional study using a structured questionnaire in three major Japanese cities from August 03 to 24, 2020 to clarify the current situation of health checkups, including vaccine-preventable diseases (VPDs), among international students at Japanese universities (JUs) and Japanese language schools (JLSs). The total response rate was 36%: 69 JUs (31%) and 137 JLSs (39%). Over 90% of these institutions conducted chest X-ray screening for tuberculosis among their students, whereas only 24.6% of JUs and 15.3% of JLSs performed general blood tests for health screening. Only 14.5% and 2.2% of the JUs and JLSs, respectively, required the submission of vaccination or antibody certificates for admission. The difficulties in requesting vaccination certificates from international students are due to poor legal requirements and concerns about rising costs for schools. From 2017 to 2019, 183 international students, principally from East Asia and Southeast Asia, were infected with VPDs, particularly tuberculosis (99 cases) and varicella (71 cases). Whereas the majority of Japanese educational institutions screen international students for tuberculosis (TB) at admission, only a few institutions request proof of antibody testing relating to other VPDs or of vaccination. These findings will help formulate guidelines for checkups related to vaccination for international students required to protect the educational institutions in Japan from the spread of VPDs. In addition, providing multifaceted social support, including financial compensation for institutions and enhanced international students’ health issues, would be helpful

Conjunctivitis, the key clinical characteristic of adult rubella in Japan during two large outbreaks, 2012-2013 and 2018-2019.

BackgroundRubella virus infection mainly causes illness with mild fever, rash, and lymphadenopathy in children; however, the clinical characteristics of adult rubella are not well-known.MethodsAn observational study was conducted to compare the characteristics between adult rubella and adult non-rubella among participants aged ≥18 years, with suspected symptomatic rubella. Participants were screened for rubella-specific IgM expression using an enzyme immune assay kit, at a tertiary care hospital in Japan during two outbreaks (January 2012-December 2013 and January 2018-March 2019). Adult rubella diagnosis followed strong positive or paired rubella-specific IgM expression or positive rubella-specific reverse-transcription-polymerase chain reaction. Patients aged ResultsOverall, 82 adult rubella and 139 adult non-rubella, with a median age (interquartile range) of 31 (25-41) years and 34 (27-42) years, respectively, were included. Multivariate analysis showed that conjunctivitis (odds ratio 80.6; 95% confidence interval 13.4-486.3; P ConclusionsConjunctivitis was the key clinical symptom associated with adult rubella. For the early diagnosis of adult rubella, clinicians should focus on assessing conjunctivitis in patients

A Multi-Center, Open-Label, Randomized Controlled Trial to Evaluate the Efficacy of Convalescent Plasma Therapy for Coronavirus Disease 2019: A Trial Protocol (COVIPLA-RCT)

Background: Coronavirus disease 2019 is a global public health concern. As of December 2020, the therapeutic agents approved for coronavirus disease 2019 in Japan were limited to two drugs: remdesivir, an antiviral drug, granted a Special Approval for Emergency on 7 May 2020, and dexamethasone, which has an anti-inflammatory effect. The aim of this study is to evaluate the efficacy of convalescent plasma collected from donors who recovered from coronavirus disease 2019. Methods: This is an open-label, randomized controlled trial comprising two groups: a convalescent plasma and a standard-of-care group. Plasma administered to patients with coronavirus disease 2019 randomized in the convalescent plasma group of this trial will be plasma that has been collected and stored in an associated study. Patients with a diagnosis of mild coronavirus disease 2019 will be included in this trial. The efficacy of convalescent plasma transfusion will be evaluated by comparing the convalescent plasma group to the standard-of-care group (without convalescent plasma transfusion) with respect to changes in the viral load and other measures. The primary endpoint will be time-weighted average changes in the SARS-CoV-2 virus load in nasopharyngeal swabs from day 0 to days 3 and 5. It is hypothesized that the intervention should result in a decrease in the viral load in the convalescent plasma group until day 5. This endpoint has been used as a change in viral load has and been used as an index of therapeutic effect in several previous studies. Discussion: The proposed trial has the potential to prevent patients with mild COVID-19 from developing a more severe illness. Several RCTs of convalescent plasma therapy have already been conducted in countries outside of Japan, but no conclusion has been reached with respect to the efficacy of convalescent plasma therapy, which is likely in part because of the heterogeneity of the types of target patients, interventions, and endpoints among trials. Actually, previous clinical trials on plasma therapy have shown inconsistent efficacy and are sometimes ineffective in COVID-19 patients with severe disease, which is due to unmeasured neutralizing antibody titer in the COVID-19 convalescent plasma. To improve this issue, in this study, we measure neutralizing activity of convalescent plasma before administration and provide the plasma with high neutralizing activity to the subjects. It is hoped that this study will further evidence to support the role of convalescent plasma therapy in COVID-19

Demographic characteristics of patients according to pre-exposure rabies prophylaxis (N = 322).

Demographic characteristics of patients according to pre-exposure rabies prophylaxis (N = 322).</p