Effectiveness of primary series, first, and second booster vaccination of monovalent mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections and severe diseases during the SARS-CoV-2 omicron BA.5 epidemic in Japan: vaccine effectiveness real-time surveillance for SARS-CoV-2 (VERSUS).

BACKGROUND: This study aimed to evaluate VE of primary, first, and second booster ancestral-strain monovalent mRNA COVID-19 vaccination against symptomatic infections and severe diseases in Japan. METHODS: We conducted a test-negative case-control study. We included medically attended episodes and hospitalizations involving individuals aged ≥16 with signs and symptoms from July to November 2022, when Omicron BA.5 was dominant nationwide. To evaluate VE, we calculated adjusted ORs of vaccination among test-positive versus test-negative individuals using a mixed-effects logistic regression. RESULTS: For VE against symptomatic infections among individuals aged 16 to 59, VE of primary vaccination at > 180 days was 26.1% (95% CI: 10.6-38.8%); VE of the first booster was 58.5% (48.4-66.7%) at ≤90 days, decreasing to 41.1% (29.5-50.8%) at 91 to 180 days. For individuals aged ≥60, VE of the first booster was 42.8% (1.7-66.7%) at ≤90 days, dropping to 15.4% (-25.9-43.2%) at 91 to 180 days, and then increasing to 44.0% (16.4-62.5%) after the second booster. For VE against severe diseases, VE of the first and second booster was 77.3% (61.2-86.7%) at ≤90 days and 55.9% (23.4-74.6%) afterward. CONCLUSION: mRNA booster vaccination provided moderate protection against symptomatic infections and high-level protection against severe diseases during the BA.5 epidemic in Japan.

Nationwide Descriptive Epidemiological Study of Patients with COVID-19 Evacuated from Wuhan, China to Japan from January to February, 2020.

We investigated the epidemiological findings regarding the route of coronavirus disease 2019 (COVID-19) and infection prevention and control (IPC) measures among returnees in the emergency evacuation from Wuhan, China to Japan during the COVID-19 outbreak in 2020. A total of 12 of the 14 returnees (median age [range]: 49.5 years [29-65 years]; 9 men [75%]) had confirmed COVID-19. The proportion of returnees with COVID-19 was 12/566 (2.1%) in Flights 1-3 and 2/263 (0.8%) in Flights 4 and 5. Six patients were asymptomatic on admission, while 3 patients developed symptoms thereafter. None of the participants reported a specific history of contact with animals, going to seafood markets, or visiting medical facilities. Two patients were in contact with an individual who was confirmed or suspected of having COVID-19. Most patients resided in hotels in the center of Wuhan City, taking taxis and trains for commute. Patients relatively adhered to IPC measures such as wearing a mask and hand hygiene. However, emphasis on IPC measures such as universal masking and more rigorous avoidance of exposure risk might have been necessary to prevent infection. In addition, forced social distancing due to lockdown might have contributed to the lower infection rates in Flights 4 and 5, compared to Flights 1-3.

Impact of COVID-19 on living donor liver and kidney transplantation programs in Japan in 2020.

BACKGROUND: Although many transplant programs have been forced to suspend living donor transplants due to the emergence of coronavirus disease (COVID-19), there are relatively few real-time databases to assess center-level transplant activities. We aimed to delineate the actual impact of COVID-19 on living donor transplant programs and the resumption process in Japan. METHODS: In a nationwide survey, questionnaires were sent to 32 liver transplant programs that had performed at least more than one case of living donor liver transplantation in 2019 and 132 kidney transplant programs that had performed more than one living donor kidney transplantation in 2018. RESULTS: Thirty-one (96.9%) and 125 (94.7%) liver and kidney transplant programs responded, respectively. In the early pandemic period, 67.7% (21/31) of liver programs and 29.8% (37/125) of kidney programs were able to maintain transplant activities similar to those during the pre-pandemic period. After temporal suspension, 58.1% of kidney programs resumed their transplant activity after the number of local COVID-19 cases peaked. Establishing institutional COVID-19 screening, triage, and therapeutic management protocols was mandatory to resume transplant activity for 64.5% and 67.7% of liver and kidney programs, respectively. In the future wave of COVID-19, 67.7% of liver programs would be affected by institutional COVID-19 intensive care unit-bound patient numbers, and 55.7% of kidney programs would stop if hospital-acquired severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection spreads. CONCLUSIONS: THIS NATIONWIDE SURVEY REVEALED FOR THE FIRST TIME HOW LIVING DONOR LIVER AND KIDNEY: transplant programs changed in response to the COVID-19 pandemic in a country where living donor transplantations are predominant.

Early diagnosis of Cryptococcus neoformans var. grubii meningitis using multiplex PCR assay in an immunocompetent patient.

Cryptococcosis is an invasive fungal infection that mainly affects the lungs and central nervous system. While patients with cell-mediated immunodeficiency are at high risk of developing cryptococcosis, there have been increasing reports of cryptococcosis in immunocompetent individuals with no underlying conditions. Herein, we report a case of cryptococcal meningitis in a 55-year-old apparently immunocompetent man with a history of heavy alcohol consumption. Although the patient was initially treated for tuberculous meningitis and varicella-zoster virus induced vasculopathy due to a history of exposure to tuberculosis and a presence of stroke, a multiplex polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF) identified Cryptococcus species unexpectedly, enabling swift treatment and a favorable clinical outcome. The multiplex PCR assay, which can identify multiple pathogens simultaneously and instantly, may lead to early diagnosis and treatment by detecting unanticipated pathogens. Furthermore, the strain was identified through multilocus sequence typing (MLST) analysis as Cryptococcus neoformans var. grubii, Sequence Type 5, molecular type: VNI. Although simplified microbial identification techniques such as mass spectrometry have recently been developed, molecular biological assays are still essential for the accurate identification of infectious strains.

SARS-CoV-2 Screening Test for Japanese Returnees From Wuhan, China, January 2020.

BACKGROUND: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) was found to be the causative microorganism of coronavirus disease 2019 (COVID-19), which started to spread in Wuhan, China. This study was to evaluate the effectiveness of questionnaire, symptoms-based screening, and polymerase chain reaction (PCR) screening of returnees from COVID-19-endemic areas on a chartered flight, to examine the proportion of infected persons and the proportion of asymptomatic persons among infected persons who returned from Wuhan. METHODS: A retrospective cohort study was done in 7 tertiary medical institutions in Japan. A total of 566 Japanese who returned from Wuhan participated in the study. RESULTS: Overall, 11 of the 566 passengers had a positive SARS-CoV-2 PCR result for pharyngeal swabs and 6 were asymptomatic. Only fever differed between SARS-CoV-2-positive and -negative individuals (P < .043). Six of the 11 PCR-positive individuals were asymptomatic; 4 remained positive on day 10, and 1 asymptomatic person tested positive up to day 27. Two of the 11 were negative on the first PCR test and positive on the second. CONCLUSIONS: Our results will be important insights on screening returnees from locked-down cities, as well as providing important data on the proportion of asymptomatic individuals infected with SARS-CoV-2. A 13-day observation period and a second round of PCR may be effective to screen patients, including asymptomatic infections.

Inflammasome expression and cytomegalovirus viremia in critically ill patients with sepsis.

BACKGROUND: CMV viremia is a contributor to poor outcomes in critically ill patients with sepsis. OBJECTIVES: To assess the expression levels of genes encoding inflammasome-related proteins in the development of CMV viremia in critically ill patients with sepsis. STUDY DESIGN: A cohort of CMV-seropositive critically ill patients with sepsis due to bloodstream infection underwent weekly testing for CMV viremia. Blood samples to evaluate mRNA levels of genes encoding CASP1, ASC, NLRP1, NLRP3, and NLRP12 were collected at the time of enrollment. Clinical outcomes were assessed at 30days or until death/discharge from ICU. RESULTS: CMV viremia was documented in 27.5% (8/29) of the patients, a median of 7days after the onset of bacteremia. Patients with sepsis who developed CMV viremia had higher CASP1 although this was not statistically significant (relative mean 3.6 vs 1.8, p=0.13). Development of high grade CMV viremia however, was significantly associated with CASP1; septic patients who developed high grade CMV viremia had significantly higher CASP1than all other patients (relative mean 5.5 vs 1.8, p=0.016). CONCLUSIONS: These data document possible involvement of inflammasome in the pathogenesis of CMV. Regulating the host immune response by agents that target these genes may have implications for improving CMV-related outcomes in these patients.

Discontinuation of Systematic Surveillance and Contact Precautions for Vancomycin-Resistant Enterococcus (VRE) and Its Impact on the Incidence of VRE faecium Bacteremia in Patients with Hematologic Malignancies.

OBJECTIVE To study the effect of discontinuation of systematic surveillance for vancomycin-resistant Enterococcus (VRE) and contact isolation of colonized patients on the incidence of VRE bacteremia SETTING A hematology-oncology unit with high prevalence of VRE colonization characterized by predominantly sporadic molecular epidemiology PARTICIPANTS Inpatients with hematologic malignancies and recipients of hematopoietic stem cell transplantation METHODS The incidence of VRE bacteremia was measured prospectively during 2 different 3-year time periods; the first during active VRE surveillance and contact precautions and the second after discontinuation of these policies. We assessed the collateral impact of this policy change on the incidence of bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile infection even though we maintained contact precautions for these organisms. Incidence of infectious events was measured as number of events per 1,000 patients days per month. Time series analysis was used to evaluate trends. RESULTS The incidence of VRE bacteremia remained stable after discontinuation of VRE surveillance and contact precautions. The incidence of MRSA bacteremia and Clostridium difficile infection for which we continued contact precautions also remained stable. Aggregated antibiotic utilization and nursing hours per patient days were similar between the 2 study periods. CONCLUSION Active surveillance and contact precautions for VRE colonization did not appear to prevent VRE bacteremia in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation with high prevalence of VRE characterized by predominantly sporadic molecular epidemiology.

Culture and medical decision making: Healthcare consumer perspectives in Japan and the United States.

OBJECTIVE: Two studies identified core value influences on medical decision-making processes across and within cultures. METHODS: In Study 1, Japanese and American adults reported desired levels of medical decision-making influence across conditions that varied in seriousness. Cultural antecedents (interdependence, independence, and power distance) were also measured. In Study 2, American adults reviewed a colorectal cancer screening decision aid. Decision preparedness was measured along with interdependence, independence, and desire for medical information. RESULTS: In Study 1, higher interdependence predicted stronger desire for decision-making information in both countries, but was significantly stronger in Japan. The path from information desire to decision-making influence desire was significant only in Japan. The independence path to desire for decision-making influence was significant only in the United States. Power distance effects negatively predicted desire for decision-making influence only in the United States. For Study 2, high (low) interdependents and women (men) in the United States felt that a colorectal cancer screening decision aid helped prepare them more (less) for a medical consultation. Low interdependent men were at significantly higher risk for low decision preparedness. CONCLUSIONS: Study 1 suggests that Japanese participants may tend to view medical decision-making influence as an interdependent, information sharing exchange, whereas American respondents may be more interested in power sharing that emphasizes greater independence. Study 2 demonstrates the need to assess value influences on medical decision-making processes within and across cultures and suggests that individually tailored versions of decision aids may optimize decision preparedness.

The inflammasome regulatory pathway and infections: role in pathophysiology and clinical implications.

The innate immune system serves to generate immediate host defenses against pathogens. Advance in the mechanism of innate immunity has provided new insights into host-pathogen microbial interactions. The cytosolic multi-protein complex called the inflammasome, which regulates the caspase-1 dependent processing of inflammatory cytokines IL-1ß and IL-18, is critical for the innate defense against pathogens. We summarize the current knowledge regarding the regulatory functions of the inflammasome in the pathogenesis of infections by various microbes (e.g., bacteria, fungi, viruses, and protozoa), and discuss its potential application in a clinical setting. Understanding of the unique role of the inflammasome signaling pathway in initiating and regulating inflammation is pivotal for the development of innovative approaches to optimize management of these infections.

Geographic differences in disease expression of cryptococcosis in solid organ transplant recipients in the United States.

BACKGROUND: Whether there are geographic differences in clinical presentation of cryptococcosis in solid organ transplant (SOT) recipients in the United States (US) is not known. MATERIAL/METHODS: Patients comprised a cohort of 120 SOT recipients from US transplant centers who fulfilled the EORTC/MSG criteria for cryptococcal disease. RESULTS: Central nervous system, pulmonary, and cutaneous cryptococcal disease were observed in 51% (61/120), 64% (77/120), and 15% (18/120) of the patients, respectively. Cutaneous disease was documented in 9% (3/32) of the patients from South Atlantic region, 19% (6/32) from Mid Atlantic, 26% (6/23) from Southern, 7% (2/29) from Midwestern, and in 1 of 4 patients from the Northwestern region of the US. When controlled for age, immunosuppressive regimen, type of transplant, and renal failure at baseline, patients from the Southern compared with other regions of the US were significantly more likely to have cutaneous cryptococcal disease (OR 3.8, 95% CI 1.1-14, P=0.045). CONCLUSIONS: Post-transplant cryptococcosis is more likely to present with cutaneous disease in the Southern region compared with other regions in the US. This predilection for cutaneous cryptococcosis could not be explained on the basis of differences in immunosuppression or the type of transplant. Whether our findings are related to strain-related variations in characteristics of the yeast or other transplant variables remains to be determined.

Identifying predictors of central nervous system disease in solid organ transplant recipients with cryptococcosis.

BACKGROUND: Cerebrospinal fluid (CSF) analysis is often deferred in patients with cryptococcal disease, particularly in the absence of neurologic manifestations. We sought to determine whether a subset of solid organ transplant (SOT) recipients with high likelihood of central nervous system (CNS) disease could be identified in whom CSF analysis must be performed. METHODS: Patients comprised a multicenter cohort of SOT recipients with cryptococcosis. RESULTS: Of 129 (88%) of 146 SOT recipients with cryptococcosis who underwent CSF analysis, 80 (62%) had CNS disease. In the overall study population, abnormal mental status, time to onset of cryptococcosis more than 24 months posttransplantation (late-onset disease), serum cryptococcal antigen titer more than 1:64, and fungemia were independently associated with an increased risk of CNS disease. Of patients with abnormal mental status, 95% had CNS cryptococcosis. When only patients with normal mental status were considered, three predictors (serum antigen titer >1:64, fungemia, and late-onset disease) independently identified patients with CNS cryptococcosis; the risk of CNS disease was 14% if none, 39% if one, and 94% if two of the aforementioned predictors existed (chi for trend P<0.001). CONCLUSIONS: CSF analysis should be strongly considered in SOT recipients with cryptococcosis who have late-onset disease, fungemia, or serum cryptococcal antigen titer more than 1:64 even in the presence of normal mental status.

Colitis as a manifestation of infliximab-associated disseminated cryptococcosis.

The ability of tumor necrosis factor (TNF)-alpha inhibitors to impair pivotal pro-inflammatory host defenses may facilitate the development of disseminated cryptococcosis. Gastrointestinal (GI) tract disease is an unusual presentation of this yeast infection. We describe a unique case of disseminated cryptococcosis presenting as colitis that mimicked an exacerbation of Crohn's disease in a TNF-alpha inhibitor recipient. Review of existing literature shows that in immunocompromised patients, GI cryptococcosis invariably coexists with disseminated cryptococcosis, often lacks prominent GI symptomatology, and is primarily diagnosed postmortem. In cases with opportunistic infections, discontinuation of TNF-alpha inhibitors is a common practice, however rapid rebound of inflammatory responses may incur the risk of immune reconstitution syndrome.

Cytomegalovirus infection in critically ill patients: a systematic review.

INTRODUCTION: The precise role of cytomegalovirus (CMV) infection in contributing to outcomes in critically ill immunocompetent patients has not been fully defined. METHODS: Studies in which critically ill immunocompetent adults were monitored for CMV infection in the intensive care unit (ICU) were reviewed. RESULTS: CMV infection occurs in 0 to 36% of critically ill patients, mostly between 4 and 12 days after ICU admission. Potential risk factors for CMV infection include sepsis, requirement of mechanical ventilation, and transfusions. Prolonged mechanical ventilation (21 to 39 days vs. 13 to 24 days) and duration of ICU stay (33 to 69 days vs. 22 to 48 days) correlated significantly with a higher risk of CMV infection. Mortality rates in patients with CMV infection were higher in some but not all studies. Whether CMV produces febrile syndrome or end-organ disease directly in these patients is not known. CONCLUSIONS: CMV infection frequently occurs in critically ill immunocompetent patients and may be associated with poor outcomes. Further studies are warranted to identify subsets of patients who are likely to develop CMV infection and to determine the impact of antiviral agents on clinically meaningful outcomes in these patients.