Transmission of SARS-CoV-2 during a 2-h domestic flight to Okinawa, Japan, March 2020.

BACKGROUND: Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has rapidly spread globally. Potentially infected individuals travel on commercial aircraft. Thus, this study aimed to investigate and test the association between the use of face masks, physical distance, and COVID-19 among passengers and flight attendants exposed to a COVID-19 passenger in a domestic flight. METHODS: This observational study investigated passengers and flight attendants exposed to COVID-19 on March 23, 2020, on board a flight to Naha City, Japan. Secondary attack rates were calculated. Whole-genome sequencing of SARS-CoV-2 was used to identify the infectious linkage between confirmed cases in this clustering. The association between confirmed COVID-19 and proximity of passengers' seats to the index case and/or the use of face masks was estimated using logistic regression. RESULTS: Fourteen confirmed and six probable cases were identified among passengers and flight attendants. The secondary attack rate was 9.7%. Twelve of 14 SARS-CoV-2 genome sequences in confirmed cases were identical to that of the index case or showed only one nucleotide mutation. Risk factors for infection included not using a face mask (adjusted odds ratio [aOR]: 7.29, 95% confidence interval [95% CI]: 1.86-28.6), partial face mask use (aOR: 3.0, 95% CI: 0.83-10.8), and being seated within two rows from the index patient (aOR: 7.47, 95% CI: 2.06-27.2). CONCLUSION: SARS-CoV-2 was transmitted on the airplane. Nonuse of face masks was identified as an independent risk factor for contracting COVID-19 on the airplane.

Performance of laboratory tests for detection for Clostridioides difficile: A multicenter prospective study in Japan.

BACKGROUND: The optimal and practical laboratory diagnostic approach for detection of Clostridioides difficile to aid in the diagnosis of C. difficile infection (CDI) is controversial. A two-step algorithm with initial detection of glutamate dehydrogenase (GDH) or nucleic acid amplification test (NAAT) alone are recommended as a predominant method for C. difficile detection in developed countries. The aim of this study was to compare the performance of enzyme immunoassays (EIA) detecting toxins A and B, NAAT detecting the toxin B gene, and GDH compared to toxigenic culture (TC) for C. difficile as the gold standard, in patients prospectively and actively assessed with clinically significant diarrhea in 12 medical facilities in Japan. METHODS: A total of 650 stool specimens were collected from 566 patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h. EIA and GDH were performed at each hospital, and NAAT and toxigenic C. difficile culture with enriched media were performed at the National Institute of Infectious Diseases. All C. difficile isolates recovered were analyzed by PCR-ribotyping. RESULTS: Compared to TC, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EIA were 41%, 96%, 75% and 84%, respectively, and for NAAT were 74%, 98%, 91%, and 92%, respectively. In 439 specimens tested with GDH, the sensitivity, specificity, PPV, and NPV were 73%, 87%, 65%, and 91%, and for an algorithm (GDH plus toxin EIA, arbitrated by NAAT) were 71%, 96%, 85%, and 91%, respectively. Among 157 isolates recovered, 75% of isolates corresponded to one of PCR-ribotypes (RTs) 002, 014, 018/018", and 369; RT027 was not isolated. No clear differences in the sensitivities of any of EIA, NAAT and GDH for four predominant RTs were found. CONCLUSION: The analytical sensitivities of NAAT and GDH-algorithm to detect toxigenic C. difficile in this study were lower than most previous reports. This study also found low PPV of EIAs. The optimal method to detect C. difficile or its toxins to assist in the diagnosis of CDI needs further investigation.

Clostridioides (Clostridium) difficile infection burden in Japan: A multicenter prospective study.

Clostridioides (Clostridium) difficile is the leading cause of healthcare-associated infectious diarrhea in the developed world. Retrospective studies have shown a lower incidence of C. difficile infection (CDI) in Japan than in Europe or North America. Prospective studies are needed to determine if this is due lack of testing for C. difficile or a true difference in CDI epidemiology. A prospective cohort study of CDI was conducted from May 2014 to May 2015 at 12 medical facilities (20 wards) in Japan. Patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h were enrolled. CDI was defined by positive result on enzyme immunoassay for toxins A/B, nucleic acid amplification test for the toxin B gene or toxigenic culture. C. difficile isolates were subjected to PCR-ribotyping (RT), slpA-sequence typing (slpA-ST), and antimicrobial susceptibility testing. The overall incidence of CDI was 7.4/10,000 patient-days (PD). The incidence was highest in the five ICU wards (22.2 CDI/10,000 PD; range: 13.9-75.5/10,000 PD). The testing frequency and CDI incidence rate were highly correlated (R2 = 0.91). Of the 146 isolates, RT018/018″ was dominant (29%), followed by types 014 (23%), 002 (12%), and 369 (11%). Among the 15 non-ICU wards, two had high CDI incidence rates (13.0 and 15.9 CDI/10,000 PD), with clusters of RT018/slpA-ST smz-02 and 018"/smz-01, respectively. Three non-RT027 or 078 binary toxin-positive isolates were found. All RT018/018" isolates were resistant to moxifloxacin, gatifloxacin, clindamycin, and erythromycin. This study identified a higher CDI incidence in Japanese hospitals than previously reported by actively identifying and testing patients with clinically significant diarrhea. This suggests numerous patients with CDI are being overlooked due to inadequate diagnostic testing in Japan.

Childhood leptospirosis in an industrialized country: Population-based study in Okinawa, Japan.

Leptospirosis is considered underdiagnosed because of its nonspecific presentation and lack of proper understanding of its epidemiology. Early diagnosis and treatment are crucial. However, few data are available on confirmed leptospirosis cases in children in industrialized countries. We therefore aimed to describe epidemiologic and clinical characteristics of laboratory-confirmed childhood leptospirosis in Okinawa, Japan. We reviewed the national surveillance data of pediatric leptospirosis in Okinawa, Japan from January 2003 through December 2015. The database included all of laboratory-confirmed leptospirosis diagnosed at the only central laboratory for leptospirosis in the region. There were 44 children (0-20 years of age) with laboratory-confirmed leptospirosis. Of these, 90% were male, 91% were 10-20 years of age, and 96% of cases occurred in August and September. The number of laboratory-confirmed patients ranged from 0 to 11 per year (mean: 3.3 per year), and the estimated annual rate was 1.0 per 100,000 pediatric populations. In all cases, the presumed infection route was recreational exposure to river water. Commonly observed manifestations include fever (95%), myalgia (52%), and conjunctival suffusion (52%). Childhood leptospirosis in Okinawa, Japan occurred predominantly in teenage boys after freshwater exposure in summer, and most patients had characteristic conjunctival suffusion. Cohort studies would be helpful to better understand more detailed clinical manifestations in association with prognosis.

Preparedness at Japan's Hospitals Designated for Patients with Highly Infectious Diseases.

In 2015, in order to assess the preparedness of Japan's special hospitals that have been designated to admit and treat patients with highly infectious diseases, we conducted a cross-sectional study of all 47 hospitals with this designation, using a self-report questionnaire that addressed 5 issues: (1) hospital characteristics and the occupation of the respondents; (2) the availability and content of the hospital guidelines for managing patients with suspected or confirmed viral hemorrhagic fever; (3) the implementation of preparedness activities in the context of the recent Ebola crisis; (4) characteristics of admission rooms for patients; and (5) human resources and occupational issues. Although our study found that most of Japan's designated hospitals were well-equipped, several areas of concern were also identified, including the lack of an effective clinical protocol, problems with management of human resources, and occupational issues. Developing a more feasible response protocol to any possible outbreak of new or reemergent infectious diseases is essential not only for Japan but for the global community in view of the threat posed by highly infectious diseases.

A Novel Drug-Resistant HIV-1 Circulating Recombinant Form CRF76_01B Identified by Near Full-Length Genome Analysis.

HIV-1 CRF01_AE and subtype B (B) have dominated and their different circulating recombinant forms (CRFs) have emerged in East and Southeast Asian countries. Here, we report a novel drug-resistant HIV-1 CRF. Five independent recombinant specimens exhibiting discordant subtype results for the gag, pol, and env sequences were isolated. These recombinants had the CRF01_AE (gag p17)/B (pol PR-RT and IN)/CRF01_AE (env C2-V3) pattern similar to CRF69_01B. Sequence analysis of four near full-length HIV-1 genomes revealed a unique phylogenetic cluster distinct from previously reported CRFs. Of the four recombinants, three shared an identical mosaic structure including seven breakpoints in the gag, pol, vif, and env regions, designated CRF76_01B. The one remaining recombinant had additional recombination breakpoints in the vpu region and exhibited another unique recombinant form composed of CRF76_01B and B. These findings provide important insight into the transmission dynamics of HIV-1 in Asia that may be important for its effective prevention.

Kudoa septempunctata-induced gastroenteritis in humans after flounder consumption in Japan: a case-controlled study.

Raw fish consumption is increasing worldwide. Since around the year 2000, western regions of Japan have reported a foodborne disease of unknown cause that occurred after the consumption of flounder. In October 2010, a particularly large outbreak was reported in these regions among individuals who consumed flounder fish that had been raised in aquaculture systems. The median incubation period was 5 h (range, 4-19 h), and the most frequently reported symptom was diarrhea (80%). The risk estimate of the consumption of flounder was significantly higher than that of the development of symptoms (odds ratio=9.50; 95% confidence interval, 1.59-∞). According to a trace-back investigation, all of the flounder responsible for the outbreak were raised in aquaculture systems. Microscopic examination revealed that the median amount of Kudoa septempunctata present in the muscle of flounder fish from the aquaculture farm was 4.5×10(3) spores/g (range, 1.0×10(3)-9.6×10(6) spores/g). The number of K. septempunctata spores required for the development of illness, as estimated using the Monte Carlo simulation, was 7.2×10(7) spores/g; therefore, thus this might be the minimum ingestion threshold for the development of gastrointestinal symptoms. As a public health measure, the current study results should be referred to for the prevention of the gastrointestinal symptoms related to the consumption of flounder; the national public health authority has disseminated these results. We concluded that K. septempunctata-contaminated flounder fish were associated with the gastrointestinal symptoms of this recent outbreak.

Association between seasonal influenza vaccination in 2008-2009 and pandemic influenza A (H1N1) 2009 infection among school students from Kobe, Japan, April-June 2009.

We assessed the effect of seasonal trivalent inactivated influenza vaccination (TIV) on pandemic influenza 2009 (pH1N1)-related illness from April to June 2009 among 2849 students (aged 12-18 years). TIV was associated with an increase in the frequency of pH1N1-related illness among subjects (adjusted odds ratio, 1.47; 95% confidence interval, 1.14-1.89). TIV during the 2008-2009 season increased the risk of pH1N1-related illness from April to June 2009.

Seroprevalence of antibodies to pandemic (H1N1) 2009 influenza virus among health care workers in two general hospitals after first outbreak in Kobe, Japan.

OBJECTIVE: To assess the prevalence including asymptomatic infection, infection risk of exposure to patients, and effectiveness of personal protective equipment (PPE) among health care workers (HCWs) during the first pandemic (H1N1) 2009 (pH1N1) outbreak in Kobe, Japan in May 2009. METHODS: A cross-sectional seroepidemiological study was conducted on 268 HCWs in the two hospitals in Kobe to which all pH1N1 inpatients were directed. Participating HCWs completed a self-administrated questionnaire and provided a single serum sample which was analyzed using a hemagglutination-inhibition (HI) antibody test. RESULTS: Of 268 subjects, 14 (5.2%) were found to have positive antibodies to the pH1N1 by HI assay; only 1 reported a febrile episode. Among the 14 seropositive cases, 8 received chemoprophylaxis. 162 HCWs (60.4%) had been exposed to patients. The seropositive rate (SPR) for pH1N1 of the exposed group was higher than that of the unexposed group, however not statistically significant (6.8% vs. 3.1%, p = 0.197). There were no statistically significant differences in SPR for any PPE. CONCLUSION: The SPR for pH1N1 in the exposed group was higher than that of the unexposed group in HCWs; however, most of these individuals were asymptomatic. There was no statistically significant association between PPE implementation and pH1N1 seropositivity.

Diagnosis of acute leptospirosis.

Leptospirosis is a globally important zoonotic disease and an important public health problem in developing countries. Early diagnosis is essential because antibiotic treatment is most effective when initiated early in the course of the disease. Culture and the microscopic agglutination test are gold standard methods for leptospirosis diagnosis; however, they are not useful for early diagnosis. Current whole cell-based rapid serological tests have low sensitivity for early phase leptospirosis and may have low specificity in highly endemic areas. PCR is demonstrably useful for early diagnosis, but it is unavailable in most developing countries. Thus, diagnostic methods that not only have higher sensitivity and accuracy for early phase leptospirosis but are also widely applicable in developing countries remain to be developed. The availability of genome sequences and genetic tools of Leptospira spp. will accelerate our understanding of Leptospira pathogenesis and provide insights into the development of more efficient and accurate diagnostic tests for acute-phase leptospirosis.