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Abstract Residents in nursing homes face heightened COVID-19 risks. We aimed to assess the adverse events (AEs) rates and antibody responses after the first to the fifth dose of COVID-19 mRNA vaccination in a nursing home cohort. Ninety-five SARS-CoV-2 naïve participants consisted of 26 staff (median age, 51 years) and 69 residents (median age, 88 years). Life-threatening AEs were reported in neither residents nor staff. The severity of non-life-threatening AEs was graded, and severe AEs were reported only in staff. The AEs rates were considerably lower in residents, compared to those in staff. Anti-RBD IgG and the neutralizing titers (NTs) against Wuhan and Omicron BA.4/BA.5 did not differ significantly between those with ‘any AE’ and ‘no AE’ among both staff and residents two months after the second, third and fifth doses, while the anti-RBD IgG significantly differed between two groups after third dose in residents. These findings suggest that the anti-RBD IgG and the NTs increase regardless of the occurrence of AEs. Our study underscores a robust antibody response in both in staff and residents, and fewer AEs following COVID-19 vaccination in SARS-CoV-2 naïve residents than staff, supporting the recommendation for mRNA booster doses in older adults at high-risk care facilities.

Case 1: A 71-year-old man was admitted to our hospital with progressive fever and dyspnea, which had developed three days after the onset of COVID-19. Initial chest computed tomography (CT) revealed a pulmonary lesion consistent with a secondary bacterial infection. Streptococcus pyogenes was isolated from cultures of primary sputum collected from the endotracheal tube, and identified as the causative microorganism. Case 2: A 91-year-old man was transferred to our hospital with severe hypotension, which had developed nine days after the onset of COVID-19. A chest CT revealed pericardial effusion and pericardiocentesis yielded purulent fluid. S. pyogenes was isolated from the fluid specimens and was identified as the causative microorganism of the secondary bacterial pericarditis. Isolates from both patients were subsequently identified as M1UK-lineage S. pyogenes via genetic analysis. This report implicates COVID-19 as a potential risk factor for severe M1UK infection via the respiratory tract.

ABSTRACT: Objective: We aimed to investigate the impact of preceding seasonal influenza on the clinical characteristics of adult patients with invasive pneumococcal disease (IPD) in Japan. Methods: Data for 1722 adult patients with IPD were analyzed before (2017-2019) and during the COVID-19 pandemic (2020-2022). Results: The seasonal influenza epidemic disappeared soon after the emergence of the pandemic. Compared with that before the pandemic (66.7%), we observed a lower bacteremic pneumonia proportion in patients with IPD during the pandemic (55.6%). The clinical presentations of IPD cases significantly differed between those with and without preceding influenza. The proportion of bacteremic pneumonia was higher in IPD patients with preceding influenza than in those without in both younger (44.9% vs 84.2%) and older adults (65.5% vs 87.0%) before the pandemic. The case fatality rate was significantly higher in IPD patients with preceding influenza (28.3%) than in those without (15.3%) in older adults before the pandemic (P = 0.020).Male and aging are high risk factors for death in older patients with IPD who had preceding influenza. Conclusion: Our study reveals that preceding seasonal influenza plays a role in the development of bacteremic pneumococcal pneumonia, increasing the risk of death in older adults.

ABSTRACTPublic bath facilities are a major source of Legionella infections in Japan. In this study, we performed 16S rRNA gene amplicon sequencing to characterize the bacterial community in bath and shower water from public bath facilities, along with chemical parameters, and investigated the effect of the bacterial microbiome on the presence of Legionella species. Although no significant difference in bacterial community richness was observed between bath and shower water samples, there was a remarkable difference in the bacterial community structure between them. Distance-based redundancy analysis revealed that several factors (free residual chlorine, pH, and conductivity) were correlated with the bacterial community in bath water. The most abundant bacterial genera in the samples were Pseudomonas (13.7%) in bath water and Phreatobacter (13.6%) in shower water, as indicated by the taxonomic composition, and the dominant bacteria differed between these environmental samples. Legionella pneumophila was the most frequently detected Legionella species, with additional 15 other Legionella species detected in water samples. In Legionella-positive water samples, several unassigned and uncultured bacteria were enriched together. In addition, the co-occurrence network showed that Legionella was strongly interconnected with two uncultured bacteria. Corynebacterium and Sphingomonas negatively correlated with Legionella species. The present study reveals the ecology of Legionella species, especially their interactions with other bacteria that are poorly understood to date.IMPORTANCEPublic bath facilities are major sources of sporadic cases and outbreaks of Legionella infections. Recently, 16S rRNA gene amplicon sequencing has been used to analyze bacterial characteristics in various water samples from both artificial and natural environments, with a particular focus on Legionella bacterial species. However, the relationship between the bacterial community and Legionella species in the water from public bath facilities remains unclear. In terms of hygiene management, it is important to reduce the growth of Legionella species by disinfecting the water in public bath facilities. Our findings contribute to the establishment of appropriate hygiene management practices and provide a basis for understanding the potential health effects of using bath and shower water available in public bath facilities.

Pigs are the most common amplifying hosts of the Japanese encephalitis virus (JEV). In 2016, four residents on Tsushima Island who did not own pig farms were diagnosed with JE. Therefore, a serosurvey was conducted to estimate the risk and seroprevalence of JEV after the outbreak. Sera collected from 560 Tsushima Island residents between January and September 2017 were tested for neutralizing antibodies against JEV strains JaGAr01 (genotype 3) and Muar (genotype 5). Sera collected from six wild boars between June and July 2022 were tested. The seroprevalence rates of neutralizing antibodies against JaGAr01 and Muar were 38.8% and 24.6%, respectively. High anti-JEV neutralizing antibody titers of ≥320 were identified in 16 residents, including 3 younger than 6 years with prior JEV vaccination, 2 in their 40s, and 11 older than 70. However, no anti-JEV-specific IgM was detected. Residents who engaged in outdoor activities had higher anti-JEV antibody titers. Sera from wild boars were negative for JEV RNA, but four of six samples contained neutralizing antibodies against JEV. Therefore, JEV transmission continues on Tsushima Island, even in the absence of pig farms, and wild boars might serve as the amplifying hosts.

Abstract SARS-CoV-2 enters host cells through the angiotensin converting enzyme 2 (ACE2) receptor and/or transmembrane protease, serine 2 (TMPRSS2). In this study, we investigated whether proteases increased SARS-CoV-2 infectivity using pseudotyped viruses and clinical specimens from patients with COVID-19. First, we investigated how trypsin increased infectivity using the pseudotyped virus. Our findings revealed that trypsin increased infectivity after the virus was adsorbed on the cells, but no increase in infectivity was observed when the virus was treated with trypsin. We examined the effect of trypsin on SARS-CoV-2 infection in clinical specimens and found that the infectivity of the SARS-CoV-2 delta variant increased 36,000-fold after trypsin treatment. By contrast, the infectivity of SARS-CoV-2 omicron variant increased to less than 20-fold in the clinical specimens. Finally, using five clinical specimens containing delta variants, enhancement of viral infectivity was evaluated in the presence of the culture supernatant of several anaerobic bacteria. As a result, viral infectivities of all the clinical specimens containing culture supernatants of Fusobacterium necrophorum were significantly increased from several- to tenfold. Because SARS-CoV-2 infectivity increases in the oral cavity, which may contain anaerobic bacteria, keeping the oral cavities clean may help prevent SARS-CoV-2 infection.

We present the clinical course of a 72-year-old female with COVID-19 and a history of hematologic stem cell transplantation for acute myeloid leukemia. We performed serial analyses of viral load and whole-genome amplification. The virus growth was evaluated by a real-time polymerase chain reaction assay. Neutralizing activity was measured using a chemiluminescence reduction neutralizing test of SARS-CoV-2 pseudotyped virus. After neutralizing antibody therapy, the cycle threshold value of viral genome was 28. Viruses were no longer isolated in a cell culture. K129R, V722I, and V987F of amino acid mutation in spike protein region were identified, although they soon disappeared. Four months after symptom onset, E340K, K356R, R346T, and E484V mutations appeared and persisted. The viability of the virus decreased over time, with the virus at day 145 having a cycle threshold value of 24 and positive virus isolation, but at a slower growth rate. Neutralizing antibody activity for Omicron BA.5 finally appeared about 4 months after infection. In immunocompromised patients, persistent infection with amino acid mutations can occur without neutralizing antibodies. However, the production of neutralizing antibodies reduces the growth rate of the SARS-CoV-2. Moreover, infection control requires attention to viral dynamics and evolution under different conditions.

Abstract It has been revealed that SARS-CoV-2 can be efficiently isolated from clinical specimens such as nasal/nasopharyngeal swabs or saliva in cultured cells. In this study, we examined the efficiency of viral isolation including SARS-CoV-2 mutant strains between nasal/nasopharyngeal swab or saliva specimens. Furthermore, we also examined the comparison of viral isolation rates by sample species using simulated specimens for COVID-19. As a result, it was found that the isolation efficiency of SARS-CoV-2 in the saliva specimens was significantly lower than that in the nasal/nasopharyngeal swab specimens. In order to determine which component of saliva is responsible for the lower isolation rate of saliva specimens, we tested the abilities of lactoferrin, amylase, cathelicidin, and mucin, which are considered to be abundant in saliva, to inhibit the infection of SARS-CoV-2 pseudotyped viruses (SARS-CoV-2pv). Lactoferrin and amylase were found to inhibit SARS-CoV-2pv infection. In conclusion, even if the same number of viral genome copies was detected by the real-time RT-PCR test, infection of SARS-CoV-2 present in saliva is thought to be inhibited by inhibitory factors such as lactoferrin and amylase, compared to nasal/nasopharyngeal swab specimens.

To determine the effects of age and variants of concern on transmission of SARS-CoV-2, we analyzed infection rates among close contacts over 4 periods in Toyama Prefecture, Japan. Among household contacts, odds of infection were 6.2 times higher during the period of the Omicron variant than during previous periods, particularly among children and adolescents.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection caused by the SFTS virus (SFTSV), with a high fatality rate of approximately 30% in humans. In recent years, cases of contact infection with SFTSV via bodily fluids of infected dogs and cats have been reported. In this study, clinical and virological analyses were performed in two dogs in which SFTSV infection was confirmed for the first time in the Toyama prefecture. Both dogs recovered; however, one was severely ill and the other mildly ill. The amount of the SFTSV gene was reduced to almost similar levels in both dogs. In the dogs’ sera, the SFTSV gene was detected at a low level but fell below the detection limit approximately 2 weeks after onset. Notably, the SFTSV gene was detected at levels several thousand times higher in urine than in other specimens from both dogs. Furthermore, the gene was detected in the urine for a long period of >2 months. The clinical signs disappeared on days 1 or 6 after onset, but infectious SFTSV was detected in the urine up to 3 weeks later. Therefore, it is necessary to be careful about contact with bodily fluids, especially urine, even after symptoms have disappeared.

Abstract We assessed the impact of the pediatric 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in adults in Japan in 2014–2018 by comparing epidemiological characteristics of adults with invasive pneumococcal disease with (n = 222) and without (n = 1258) meningitis. The annual incidence of pneumococcal meningitis in 2016–2018 was 0.20–0.26 cases/100,000 population. Age (p

We report 2 adult cases of invasive disease in Japan caused by Streptococcus oralis that expressed the serotype 3 pneumococcal capsule and formed mucoid colonies. Whole-genome sequencing revealed that the identical serotype 3 pneumococcal capsule locus and hyl fragment were recombined into the genomes of 2 distinct S. oralis strains.

Background Streptococcus suis is a zoonotic pathogen that can cause invasive infections in humans who are in close contact with infected pigs or contaminated pork-derived products. S. suis serotype 2 sequence type (ST) 1 strains are mostly associated with meningitis, whereas ST104 strains are mostly recovered from sepsis cases in humans. No data are available for comparison of the ST1 and ST104 strains at the genomic level, particularly concerning virulence-associated genes. Thus, genomic comparison of both STs was performed in this study. Methods An ST1 isolate (ID26154) from the cerebrospinal fluid of a patient with meningitis and an ST104 isolate (ID24525) from the blood of a patient with sepsis were subjected to shotgun pyrosequencing using the 454 GS Junior System. Genomic comparison was conducted between the ST1 isolate and the ST104 isolate using the Artemis Comparison Tool (ACT) to identify the region of differences (RDs) between ST1 and ST104. Results Fifty-eight RDs were unique to the ST104 genome and were mainly involved in metabolism and cell functional activities, cell wall anchored proteins, bacteriophages and mobile genetic elements, ABC-type transporters, two-component signal transductions, and lantibiotic proteins. Some virulence genes mostly found in ST1 strains were also present in the ST104 genome. Whole-genome comparison is a powerful tool for identifying genomic region differences between different STs of S. suis serotype 2, leading to the identification of the molecular basis of virulence involved in the pathogenesis of the infection.

Objective: This study aimed to describe the epidemiological and clinical characteristics of endemics of two rickettsial diseases, scrub typhus (ST) and Japanese spotted fever (JSF), in Japan. Methods: We conducted a retrospective, descriptive epidemiological assessment of cases notified via national surveillance from 2007–2016. Results: Over the 10-year period, 4185 ST and 1765 JSF cases were notified; of these, 20 (0.48%) cases of ST and 16 (0.91%) cases of JSF were fatal at the time of reporting. The elderly had higher notification rates and fatalities. While the annual number of ST notifications was stable and cases were reported from a broad geographic range, the number of JSF reports increased three-fold, expanding from the southwest to the east. The seasonality of ST varied by region and was more common during spring/summer in the north and autumn/winter in the south; 78% of cases occurred during autumn/winter, mainly in the southern region. Most of the fatal ST cases occurred in the spring/summer and occurred in the northern region. Conclusion: Our analysis identified seasonal and regional variations in the distribution of rickettsiosis. These variations were most likely to be related to the ecology of the vectors and etiological agents. Knowing the recent epidemiological and clinical features of ST and JSF can support clinical diagnosis and guide preventative activities against these vector-borne diseases.

The decline in the proportion of pneumococcal conjugate vaccine (PCV)–covered serotypes among adult invasive pneumococcal disease (IPD) patients might change the overall effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) because its effectiveness differs according to serotype. Using the indirect cohort method, we calculated the effectiveness of PPSV23 against IPD among adults in Japan to assess the impact of the national pediatric PCV program. Clinical and epidemiologic information and pneumococcal isolates were collected from IPD patients >20 years of age through enhanced IPD surveillance during April 2013–December 2017. Adjusted effectiveness against PPSV23-serotype IPD was 42.2%. Despite a substantial decline in the proportion of 13-valent PCV serotypes during the study period (45% to 31%), the change in effectiveness for PPSV23-serotype IPD was limited (47.1% to 39.3%) and only marginal in the elderly population (39.9% to 39.4%). The pediatric PCV program had limited impact on PPSV23 effectiveness against IPD in adults.

An observational study to assess immunogenicity before and after the first, second, and third vaccinations with the 23-valent pneumococcal polysaccharide vaccine in a cohort of 16 elderly patients with chronic lung diseases was conducted. The safety of this vaccine was also compared between the first, second, and third vaccinations. Serotype-specific immunoglobulin G (IgG) and the opsonization index (OI) for serotypes 6B, 14, 19F, and 23F were analyzed, and adverse local and systemic reactions were compared. The levels of serotype-specific IgG and OI increased significantly 1 month after the first, second, and third vaccinations. Peak IgG levels were higher after the third vaccination than after the second vaccination, but the levels of serotypes 6B, 14, and 19F were not higher than after the first vaccination. Serotype-specific OIs did not differ after the third vaccination compared with the first and second vaccinations. The level of serotype-specific IgG required for killing 50% of bacteria decreased significantly 1 month after the second vaccination. This level was slightly elevated immediately before the third vaccination but decreased after the third vaccination. Although self-limited local and systemic reactions were more frequent after the second and third vaccinations than after the first vaccination, no serious systemic reactions were seen after any vaccination. These data suggest that sustained functional serotype-specific IgG is produced after the first, second, and third vaccinations and they confirm the safety of the second and third vaccinations in elderly people with chronic lung disease.

We conducted an epidemiologic study of severe fever with thrombocytopenia syndrome (SFTS) in Japan during 2013–2017. Of 303 cases reported during that period, 133 (44%) were included in this study. The median time between onset of illness and diagnosis of SFTS shortened, from 11.5 to 3.0 days, but the case-fatality rate remained high, at 27%. In 64 patients (48%), a close contact with companion animals was reported within 2 weeks of disease onset. Of these 64 patients, 40 were surveyed further, and we confirmed that 3 had direct contact with body fluids of ill companion animals; 2 had direct contact with the saliva of an ill feral cat or pet dog. These patients reported no history of tick bite, suggesting that ill companion animals might be a source of SFTS virus transmission. Direct contact with the body fluids of ill companion animals should be avoided.

ABSTRACT Serological tests are beneficial for recognizing the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). To identify protective immunity, optimization of the chemiluminescent reduction neutralizing test (CRNT) is critical. Whether commercial antibody tests have comparable accuracy is unknown. Serum samples were obtained from COVID-19 patients (n = 74), SARS-CoV-2 PCR-negative (n = 179), and suspected healthy individuals (n = 229) before SARS-CoV-2 variants had been detected locally. The convalescent phase was defined as the period after day 10 from disease onset or the episode of close contact. The CRNT using pseudotyped viruses displaying the wild-type (WT) spike protein and a commercial anti-receptor-binding domain (RBD) antibody test were assayed. Serology for the B.1.1.7 and B.1.351 variants was also assayed. Both tests concurred for symptomatic COVID-19 patients in the convalescent phase. They clearly differentiated between patients and suspected healthy individuals (sensitivity: 95.8% and 100%, respectively; specificity: 99.1% and 100%, respectively). Anti-RBD antibody test results correlated with neutralizing titers (r = 0.31, 95% confidence interval [CI] 0.22–0.38). Compared with the WT, lower CRNT values were observed for the variants. Of the samples with ≥100 U/mL by the anti-RBD antibody test, 77.8% and 88.9% showed ≥50% neutralization against the B.1.1.7 and the B.1.351 variants, respectively. Exceeding 100 U/mL in the anti-RBD antibody test was associated with neutralization of variants (P < 0.01). The CRNT and commercial anti-RBD antibody test effectively classified convalescent COVID-19 patients. Strong positive results with the anti-RBD antibody test can reflect neutralizing activity against emerging variants. IMPORTANCE This study provides a diagnostic evidence of test validity, which can lead to vaccine efficacy and proof of recovery after COVID-19. It is not easy to know neutralization against SARS-CoV-2 in the clinical laboratory because of technical and biohazard issues. The correlation of the quantitative anti-receptor-binding domain antibody test, which is widely available, with neutralizing test indicates that we can know indirectly the state of acquisition of functional immunity against wild and variant-type viruses in the clinical laboratory.

Introduction: In Japan, syphilis notifications have increased. Men who have sex with men (MSM) in Tokyo have contributed substantially to the increase in syphilis notifications. We thus aimed to determine the correlates of incident syphilis among them. Methods: MSM who attended a Tokyo clinic that serves sexual minorities were recruited in a case-control study in 2015. A case was seropositive for primary/secondary/asymptomatic syphilis at enrolment visit and seronegative at prior visit or had oral ulcers positive for Treponema pallidum DNA at enrolment. For each case, two controls seronegative at enrolment and prior visit were selected. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated to assess for correlates of case status. Results: Among 35 cases, the median age was 37 (range = 21–63) years and was similar to the 71 controls. Among HIV-positive participants (26 cases and 67 controls), cases were independently associated with higher frequency of anal or oral sex (OR = 3.4; 95% CI = 1.4–8.6; increase per category from < 1/month, ≥ 1/month but < 1/week, to ≥ 1/week) and no or inconsistent condom use during anal or oral sex (OR = 3.0; 95% CI = 1.1–8.3; increase per category from using every time, occasionally, to never), adjusted for residency and time between visits. Discussion: Modifiable behaviours were associated with incident syphilis, and dissemination of prevention messages are needed.

Abstract Background Active surveillance has the potential to prevent nosocomial transmission of carbapenem-resistant Acinetobacter baumannii (CRAB). We assessed whether rapid diagnosis using clinical specimen-direct loop-mediated isothermal amplification (LAMP), a rapid molecular diagnostic assay, and subsequent intervention, could reduce CRAB nosocomial transmission in intensive care units (ICUs). Methods A before and after (quasi-experimental) study was conducted in two ICUs at the Mahidol University Faculty of Medicine Ramathibodi Hospital with 3 months of observational period followed by 9 months of interventional period. All patients were screened for CRAB using both the culture and LAMP method from rectal swab and/or bronchial aspirates (intubated patients only) upon admission, weekly thereafter, and upon discharge. During the pre-intervention period, we performed contact precautions based on culture results. In contrast, during the intervention period, we initiated contact precautions within a few hours after sample collection on the basis of LAMP results. Results A total of 1335 patients were admitted to the ICUs, of which 866 patients (pre-intervention period: 187; intervention period: 679) were eligible for this study. Incidence rate of CRAB infection decreased to 20.9 per 1000 patient-days in the intervention period from 35.2 in the pre-intervention period (P

The World Health Organization recommends that countries or organizations that host mass gatherings plan ahead and prepare for possible public health events to ensure a safe environment for local residents, participants and travellers.1 Public health events during mass gatherings can also affect non-host countries. There are numerous reports of the spread of infectious diseases by travellers returning from mass gatherings,2 which can potentially pose the risk of an outbreak of new infectious diseases to travellers’ home countries. With more frequent travel across borders, it is prudent that non-host countries prepare for mass gathering events.

Context: Although the incidence of invasive pneumococcal infections in children has decreased since the introduction of pneumococcal conjugate vaccines (PCVs), the appearance of serotype replacements has continued to increase. Aims: We examined the frequency of serotype replacements in adult cases of pneumococcal pneumonia. Furthermore, the transition in the coverage of vaccine serotypes (VTs) to non-VTs (NVTs) was also examined. Settings and Design: We investigated all confirmed cases of pneumococcal pneumonia in 303 adult patients admitted to Yamagata Saisei Hospital between April 2006 and March 2015. Materials and Methods: Pneumococcal serotypes were determined by testing for a specific type of antiserum using the capsular swelling method. Statistical Analysis Used: Chi-square tests were used to compare patient characteristics. Results: Annually, the number of admitted patients ranged from 24 to 43, with most of them being men (64.7% of the total patient cohort). Although many cases involved some underlying conditions, the rate of pneumococcal vaccination remained low. The average rate of multigeneration housing was high (37.6%). The rates of pneumococcal vaccine coverage declined since 2013 (7-valent PCV (PCV7), 18.5%; PCV13, 59.3%; and 23-pneumococcal polysaccharide vaccine (PPSV23), 66.7%) and were

Pneumococcal surface protein A (PspA) is a surface protein of Streptococcus pneumoniae that may be a candidate antigen for new pneumococcal vaccines. This study investigates the distribution of PspA clades of the causative strains of adult invasive pneumococcal disease (IPD) in Japan. Of the 1,939 strains isolated from cases of adult IPD during 2014–2019, the PspA clades of 1,932 (99.6%) strains were determined, and no pspA was detected in the remaining 7 strains (0.4%). PspA clades 1–6 were detected in 786 (40.5%), 291 (15.0%), 443 (22.8%), 369 (19.0%), 33 (1.7%), and 6 (0.3%) strains, respectively. New PspA clades (0.2%) were identified in two non-typeable and two serotype 35B pneumococci. The proportions of clade 1 and clade 2 showed significantly decreased and increased trends, respectively. Furthermore, the PspA clade of pneumococcal strains was partially serotype- and sequence type-dependent. The majority of strains belonging to serotypes contained in both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) belonged to PspA clades 1 or 3. In contrast, the distribution of clades in non-vaccine serotypes was wider than that of vaccine serotype pneumococci. Our findings demonstrate that almost all pneumococcal strains from adult IPD express PspA clades 1–4, especially for non-vaccine serotypes. These results may be useful for the development of a new pneumococcal vaccine with PspA.

Outbreaks of infectious diseases can occur after natural disasters as vital services are disrupted and populations move into evacuation centres. National notifiable disease surveillance may be inadequate in these situations because of resource-consuming disease confirmation or system interruptions. Although syndromic surveillance has been used as an alternative in post-disaster situations, no systematic evaluations of it have been published. We evaluated the ad hoc paper-based syndromic surveillance system implemented in evacuation centres in Ibaraki prefecture after the 2011 Great East Japan Earthquake and Tsunami. We assessed the simplicity, acceptability, data quality, timeliness and portability of this system and reviewed its usefulness. We concluded that the system was simple, acceptable, portable and useful. The documentation and monitoring of disease events and trends were useful for developing interventions in evacuation centres and have since been used to improve post-disaster infectious disease and surveillance knowledge in Japan. We believe timeliness was a challenge due to the chain of data transmission and communication passing through an intermediary. Future implementations of this system could consider a more direct chain of data transmission and communication from collectors to analysers. Too few key informant interviewees and the inability to obtain original paper-based data from evacuation centres limited our findings; we conducted this evaluation four years after the response occurred. Future evaluations should be completed closer to when operations cease. The usefulness of the system suggests adopting it in future disasters. A simple, plain-language manual should be developed to improve future employment.

During the 2016–17 winter season in Japan, human norovirus GII.P16-GII.2 strains (2016 strains) caused large outbreaks of acute gastroenteritis. Phylogenetic analyses suggested that the 2016 strains derived from the GII.2 strains detected during 2010–12. Immunochromatography between 2016 strains and the pre-2016 GII.2 strains showed similar reactivity.

Problem: Six invasive meningococcal disease cases occurred among Scottish and Swedish nationals associated with the World Scout Jamboree (WSJ), an international mass gathering, held in Japan. The index case developed symptoms while returning home. The strains from all six cases were identical and seldom seen in Japan. Context: Over 33 000 participants from 155 countries attended WSJ. At the Jamboree site, participants of the North of Scotland’s and Sweden’s units camped within the same subcamp and kept the same schedule of events. No information was available about the Swedish and Scottish cases’ close personal contact history. Action: Health Protection Scotland investigated Scottish cases, conducted active case finding, provided chemoprophylaxis, vaccinated close contacts and advised Scottish WSJ participants and contacts to seek medical care if they developed symptoms. The Public Health Agency of Sweden recommended chemoprophylaxis to all participants in Sweden. In Japan, the Ministry of Health, Labour and Welfare (MHLW) requested the Scout Association of Japan advise all participants to seek medical attention if they developed symptoms. MHLW shared information about the event with local authorities, medical associations, and the Ministry of Education, Culture, Sports, Science and Technology. Outcome: No additional case related to WSJ has been reported. This outbreak highlighted the risk for international spread of invasive meningococcal disease at international mass gatherings. Discussion: Assessing risk, educating participants, enhancing surveillance and sharing timely information among related countries are significant for prevention and response against invasive meningococcal disease outbreaks at mass gatherings.

Field Epidemiology Training Programmes (FETPs), which are modelled after the Centers for Disease Control and Prevention’s Epidemic Intelligence Service programme, began in 1980 and have produced graduates in more than 70 countries, including 12 in the Western Pacific Region.1,2 These programmes aim to “build sustainable capacity for detecting and responding to public health threats” and “develop expertise so that disease outbreaks can be detected locally and prevented from spreading”.3 FETPs thus include training in applied epidemiology and public health services. FETP trainees and graduates, however, often have additional responsibilities: mentoring newer trainees, supervising in the field, leading short training courses, facilitating meetings, etc. Programmes therefore must provide trainees with the knowledge and skills to fulfil these responsibilities.

Genotyping evidence that supports the interruption of endemic measles virus (MV) transmission is one of the essential criteria to be verified in achieving measles elimination. In Japan since 2014, MV genotype analyses have been performed for most of the measles cases in prefectural public health institutes nationwide. With this strong molecular epidemiological data, Japan was verified to have eliminated measles in March, 2015. However, even in the postelimination era, sporadic cases and small outbreaks of measles have been detected repeatedly in Japan. This study investigated the nationwide molecular epidemiology of MV between 2008 and 2017. The 891 strains in the total period between 2008 and 2017 belonged to seven genotypes (D5, D4, D9, H1, G3, B3, and D8) and 124 different MV sequence variants, based on the 450-nucleotide sequence region of the N gene (N450). The 311 MV strains in the postelimination era between 2015 and 2017 were classified into 1, 7, 8, and 32 different N450 sequence variants in D9, H1, B3, and D8 genotypes, respectively. Analysis of the detection period of the individual N450 sequence variants showed that the majority of MV strains were detected only for a short period. However, MV strains, MVs/Osaka.JPN/29.15/ [D8] and MVi/Hulu Langat.MYS/26.11/ [D8], which are named strains designated by World Health Organization (WHO), have been detected in many cases over 2 or 3 years between 2015 and 2017. The WHO-named strains have circulated worldwide, causing outbreaks in many countries. Epidemiological investigation revealed repeated importation of these WHO-named strains into Japan. To demonstrate the elimination status (interruption of endemic transmission) in situations with repeated importation of the same strains is challenging. Nevertheless, the detailed sequence analysis of individual MV strains and chronological analysis of these strains provided sufficient evidence to show that Japan has still maintained its measles elimination status in 2017.

Escherichia albertii, a zoonotic enteropathogen, is responsible for outbreaks of disease in humans. Identifying strains of E. albertii by phenotypic characterization tests is difficult because of its poorly defined properties. Screening its phenotypic characteristics is, nevertheless, a necessary prerequisite for further genetic analysis of its properties, and species-specific polymerase chain reaction (PCR) analysis can be used to type the pathogen. While two E. albertii biogroups (1 and 2) have been described, strains with characteristics divergent from both biogroups have been reported worldwide. The aim of the present study was to evaluate the characteristics of non-biogroup 1 or 2 strains, and discern the characteristics common to all of the E. albertii strains from this study. Altogether, 107/414 field isolates were selected for examination based on pulsed-field gel electrophoresis analysis. The 107 strains were isolated from 92 sources, including humans and pigeon feces, other wild birds, and retail chicken livers. All strains were then examined using various culture-based, biochemical (API 50CHE tests, API Zym test, and others) and molecular (virulence gene screening, multi-locus sequence analysis) testing methods. Our results revealed that all field strains (n = 107) showed non-biogroup 1 or 2 characteristics, with multiple sequence differences. Variations in indole production and the lysine decarboxylase activity profiles among the isolates made identification of E. albertii very difficult. Therefore, we propose that non-biogroup 1 or 2 of E. albertii should be assigned to biogroup 3 to make screening of them easier in public health and clinical laboratory settings. Clearly, having group criteria for indole-negative/lysine-positive, indole-positive/lysine-negative, and indole-positive/lysine-positive E. albertii biogroups 1, 2, and 3 strains, respectively, should provide for more accurate identification of E. albertii isolates. Based on our findings, we recommend that isolates displaying phenotype mobility-negativity (sulfide-indole-motility medium, 37°C), hydrogen sulfide production-negativity (triple sugar iron medium), acid production-negativity from xylose, negative β-glucuronidase activity properties, and showing indole production and lysine decarboxylase activity profiles in accordance with one of the three biogroups, should be further assessed using an E. albertii-specific PCR assay.

Enhanced surveillance of invasive pneumococcal disease (IPD) in adults was conducted during April 2013-March 2018 in 10 of 47 prefectures in Japan, and a total of 1277 IPD patients were enrolled. An emergence of IPD caused by serotype 12F was identified during May 2015-March 2018 through this surveillance. 12F isolates were composed of four related sequence types. In total, 120 patients with 12F IPD were reported during this period. To characterize the clinical features of 12F IPD, the disease characteristics of these patients were compared with those of 1157 patients with non-12F IPD. Compared with the non-12F IPD patients, a significantly lower proportion of 12F IPD patients was aged 65 years or older (55% vs. 70%), vaccinated with 23-valent pneumococcal polysaccharide (4% vs. 14%), had comorbid illness (65% vs. 77%), or were immunocompromised (19% vs. 30%; all P < 0.05). No significant difference in the proportion of case fatalities was found between the two groups. The proportions of those aged 65 years or older (53% vs. 69%) and with bacteremic pneumonia (35% vs. 69%) were significantly lower in 17 patients who died from 12F IPD than in 205 patients who died from non-12F IPD (all P < 0.05). Differences in clinical features were similarly found between 12F IPD patients and patients in low- or intermediate-level invasive potential serogroups. Our data demonstrated that serotype 12F was associated with IPD in younger adults and a lower proportion of comorbid illness, including immunocompromised conditions, in adult IPD, suggesting the high invasive potential of the serotype 12F. In addition, patients who died from 12F IPD were younger and had proportionately more bacteremia without focus. These findings may provide new insight into the pathogenesis of IPD in adults caused by 12F serotype with a high invasive potential.

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5–7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases N = 32; cases = 4503), PCV13 types caused 14% in

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.

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Streptococcus suis is a zoonotic pathogen of economic significance to the swine industry. The number of infected cases is increasing in humans worldwide. In this study, we determined the prevalence and diversity of S. suis carriage in slaughterhouse pigs in Phayao province, Thailand, where an outbreak occurred in 2007. The overall S. suis carriage rate was 35.2% among slaughterhouse pigs. The prevalence rates of serotypes 2 and 14 (the major serotypes infected in humans) were 6.7% and 2.6%, respectively. In both serotypes, 70.4% of isolates of serotypes 2 and 14 revealed sequence types and pulsotypes identical to human isolates in Thailand. It is suggested that pathogenic strains of S. suis are a risk factor for occupational exposure to pigs or the consumption of raw pork products. Food safety, hygiene, and health education should be encouraged to reduce the risk group.

In the 2016/2017 winter season in Japan, HuNoV GII.P16-GII.2 strains (2016 strains) emerged and caused large outbreaks of acute gastroenteritis. To better understand the outbreaks, we examined the molecular evolution of the VP1 gene and RdRp region in 2016 strains from patients by studying their time-scale evolutionary phylogeny, positive/negative selection, conformational epitopes, and phylodynamics. The time-scale phylogeny suggested that the common ancestors of the 2016 strains VP1 gene and RdRp region diverged in 2006 and 1999, respectively, and that the 2016 strain was the progeny of a pre-2016 GII.2. The evolutionary rates of the VP1 gene and RdRp region were around 10-3 substitutions/site/year. Amino acid substitutions (position 341) in an epitope in the P2 domain of 2016 strains were not found in pre-2016 GII.2 strains. Bayesian skyline plot analyses showed that the effective population size of the VP1 gene in GII.2 strains was almost constant for those 50 years, although the number of patients with NoV GII.2 increased in 2016. The 2016 strain may be involved in future outbreaks in Japan and elsewhere.

Objective: In August 2012, an outbreak of enterohaemorrhagic Escherichia coli (EHEC) O157 infection was investigated by the City of Sapporo and Hokkaido Prefectural Government. The initial notification reported an illness affecting 94 residents of 10 private nursing homes distributed across multiple areas of Hokkaido, the northernmost island of Japan; at this time three cases were confirmed as EHEC O157 infection. The objectives of the investigation were to identify the source of infection and recommend control measures to prevent further illness. Methods: A suspected case was defined as a resident of one of the private nursing homes in Hokkaido who had at least one of the following gastrointestinal symptoms: diarrhoea, bloody stool, abdominal pain or vomiting between 10 July and 10 September 2012. Cases were confirmed by the presence of Shiga toxin 1- and 2-producing EHEC O157 in stool samples of suspected cases. We conducted an epidemiological analysis and an environmental investigation. Results: We identified 54 confirmed and 53 suspected cases in 12 private nursing homes including five fatalities. Of the 107 cases, 102 (95%) had consumed pickles, all of which had been manufactured at the same facility. EHEC O157 isolates from two pickle samples, 11 cases and two staff members of the processing company were indistinguishable. The company that produced the pickles used inadequate techniques to wash and sanitize the vegetables. Discussion: Contaminated pickles were the likely source of this outbreak. We recommended that the processing company improve their methods of washing and sanitizing raw vegetables. As a result of this outbreak, the sanitation requirements for processing pickles were revised.

In Nakhon Phanom, Thailand, we identified 38 hospitalized patients with Streptococcus suis infection during 2006–2012. Deafness developed in 12 patients; none died. Thirty-five reported recent exposure to pigs/pork. Annual incidence was 0.1–2.2 cases/100,000 population (0.2–3.2 in persons >20 years of age). Clinicians should consider S. suis infection in areas where pig exposure is common.

The discovery of highly divergent lineages of hantaviruses (family Hantaviridae) in shrews, moles, and bats of multiple species raises the possibility that non-rodent hosts may have played a significant role in their evolutionary history. To further investigate this prospect, total RNA was extracted from RNAlater®-preserved lung tissues of 277 bats (representing five families, 14 genera and 40 species), captured in Myanmar and Vietnam during 2013–2016. Hantavirus RNA was detected in two of 15 black-bearded tomb bats (Taphozous melanopogon) and two of 26 Pomona roundleaf bats (Hipposideros pomona) in Myanmar, and in three of six ashy leaf-nosed bats (Hipposideros cineraceus) in Vietnam. Pair-wise alignment and comparison of coding regions of the S, M, and L segments of hantaviruses from Taphozous and Hipposideros bats revealed high nucleotide and amino acid sequence similarities to prototype Láibīn virus (LAIV) and Xuân Sơn virus (XSV), respectively. Phylogenetic analyses, generated by maximum-likelihood and Bayesian methods, showed a geographic clustering of LAIV strains from China and Myanmar, but not of XSV strains from China and Vietnam. These findings confirm that the black-bearded tomb bat is the natural reservoir of LAIV, and that more than one species of Hipposideros bats can host XSV.

BACKGROUND:Dengue is becoming an increasing threat to non-endemic countries. In Japan, the reported number of imported cases has been rising, and the first domestic dengue outbreak in nearly 70 years was confirmed in 2014, highlighting the need for greater situational awareness and better-informed risk assessment. METHODS:Using national disease surveillance data and publically available traveler statistics, we compared monthly and yearly trends in the destination country-specific dengue notification rate per 100,000 Japanese travelers with those of domestic dengue cases in the respective country visited during 2006-2014. Comparisons were made for countries accounting for the majority of importations; yearly comparisons were restricted to countries where respective national surveillance data were publicly available. RESULTS:There were 1007 imported Japanese dengue cases (Bali, Indonesia (n = 202), the Philippines (n = 230), Thailand (n = 160), and India (n = 152)). Consistent with historic local dengue seasonality, monthly notification rate among travelers peaked in August in Thailand, September in the Philippines, and in Bali during April with a smaller peak in August. While the number of travelers to Bali was greatest in August, the notification rate was highest in April. Annually, trends in the notification rate among travelers to the Philippines and Thailand also closely reflected local notification trends. CONCLUSION:Travelers to dengue-endemic countries appear to serve as reliable "sentinels", with the trends in estimated risk of dengue infection among Japanese travelers closely reflecting local dengue trends, both seasonally and annually. Sentinel traveler surveillance can contribute to evidence-based pretravel advice, and help inform risk assessments and decision-making for importation and potentially for subsequent secondary transmission. As our approach takes advantage of traveler data that are readily available as a proxy denominator, sentinel traveler surveillance can be a practical surveillance tool that other countries could consider for implementation.

Although severe fever with thrombocytopenia syndrome (SFTS) was first reported from Japan in 2013, the precise clinical features and the risk factors for SFTS have not been fully investigated in Japan. Ninety-six cases of severe fever with thrombocytopenia syndrome (SFTS) were notified through the national surveillance system between April 2013 and September 2014 in Japan. All cases were from western Japan, and 82 cases (85%) had an onset between April and August. A retrospective observational study of the notified SFTS cases was conducted to identify the clinical features and laboratory findings during the same period. Of 96 notified cases, 49 (51%) were included in this study. Most case-patients were of advanced age (median age 78 years) and were retired or unemployed, or farmers. These case-patients had a history of outdoor activity within 2 weeks before the onset of illness. The median serum C-reactive protein concentration was slightly elevated at admission. Fungal infections such as invasive aspergilosis were found in 10% of these case-patients. Hemophagocytosis was observed in 15 of the 18 case-patients (83%) whose bone marrow samples were available. Fifteen cases were fatal, giving a case-fatality proportion of 31%. The proportion of neurological abnormalities and serum concentrations of lactate dehydrogenase and aspartate aminotransferase were significantly higher in the fatal cases than in the nonfatal cases during hospitalization. Appearance of neurological abnormality may be useful for predicting the prognosis in SFTS patients.

To examine associations between clinical features of Streptococcus suis serotype 2 infections in humans in Thailand and genotypic profiles of isolates, we conducted a retrospective study during 2006–2008. Of 165 patients for whom bacterial cultures of blood, cerebrospinal fluid, or both were positive for S. suis serotype 2, the major multilocus sequence types (STs) found were ST1 (62.4%) and ST104 (25.5%); the latter is unique to Thailand. Clinical features were examined for 158 patients. Infections were sporadic; case-fatality rate for adults was 9.5%, primarily in northern Thailand. Disease incidence peaked during the rainy season. Disease was classified as meningitis (58.9%) or nonmeningitis (41.1%, and included sepsis [35.4%] and others [5.7%]). Although ST1 strains were significantly associated with the meningitis category (p

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Healthcare-associated infections are a leading cause of morbidity and mortality worldwide. Treatment is increasingly complicated by the escalating incidence of antimicrobial resistance. Among drug-resistant pathogens, carbapenem-resistant Acinetobacter baumannii (CRAb) is of increasing concern because of the limited applicable therapies and its expanding global distribution in developed countries and newly industrialized countries. Therefore, a rapid detection method that can be used even in resource-poor countries is urgently required to control this global public health threat. Conventional techniques, such as bacterial culture and polymerase chain reaction (PCR), are insufficient to combat this threat because they are time-consuming and laborious. In this study, we developed a loop-mediated isothermal amplification (LAMP) method for detecting blaOXA-23-positive CRAb, the most prevalent form of CRAb in Asia, especially in Thailand, and confirmed its efficacy as a surveillance tool in a clinical setting. Clinical samples of sputum and rectal swabs were collected from patients in a hospital in Bangkok and used for LAMP assays. After boiling and centrifugation, the supernatants were used directly in the assay. In parallel, a culture method was used for comparison purposes to evaluate the specificity and sensitivity of LAMP. As a first step, a total of 120 sputum samples were collected. The sensitivity of LAMP was 88.6% (39/44), and its specificity was 92.1% (70/76) using the culture method as the "gold standard". When surveillance samples including sputum and rectal swabs were analyzed with the LAMP assay, its sensitivity was 100.0%. This method enables the direct analysis of clinical specimens and provides results within 40 minutes of sample collection, making it a useful tool for surveillance even in resource-poor countries.

Recently, it has been reported that circulating free DNA (cf-DNA) in the blood is increased in various infectious diseases, including sepsis. Moreover, a relationship between cf-DNA and neutrophil extracellular traps (NETs) has been suggested. However, it is still unclear what the source and physiological role of cf-DNA in sepsis are. In this study, we examined the source of cf-DNA by detecting citrullinated histone H3, a characteristic feature of NET formation, in cecal ligation and puncture- (CLP-)operated mice. In addition, neutrophil depletion using anti-Ly6G antibodies was performed to assess the association between neutrophils and cf-DNA. Increased cf-DNA levels were observed only in CLP mice and not in the control groups; the qPCR findings revealed that the cf-DNA was mainly host-derived, even in bacteremic conditions. Citrullinated histone H3 was not increased in the neutrophils upon CLP, and the depletion of neutrophils showed limited effects on decreasing the amount of cf-DNA. Taken together, these results suggested that elevated cf-DNA levels during early-phase sepsis may represent a candidate biomarker for the severity of sepsis and that, contrary to previous findings, cf-DNA is not derived from neutrophils or NETs.

Neutrophil extracellular traps (NETs), a newly identified immune mechanism, are induced by inflammatory stimuli. Modification by citrullination of histone H3 is thought to be involved in the in vitro formation of NETs. The purposes of this study were to evaluate whether NETs and citrullinated histone H3 (Cit-H3) are present in the bloodstream of critically ill patients and to identify correlations with clinical and biological parameters. Blood samples were collected from intubated patients at the time of ICU admission from April to June 2011. To identify NETs, DNA and histone H3 were visualized simultaneously by immunofluorescence in blood smears. Cit-H3 was detected using a specific antibody. We assessed relationships of the presence of NETs and Cit-H3 with the existence of bacteria in tracheal aspirate, SIRS, diagnosis, WBC count, and concentrations of IL-8, TNF-α, cf-DNA, lactate, and HMGB1. Forty-nine patients were included. The median of age was 66.0 (IQR: 52.5-76.0) years. The diagnoses included trauma (7, 14.3%), infection (14, 28.6%), resuscitation from cardiopulmonary arrest (8, 16.3%), acute poisoning (4, 8.1%), heart disease (4, 8.1%), brain stroke (8, 16.3%), heat stroke (2, 4.1%), and others (2, 4.1%). We identified NETs in 5 patients and Cit-H3 in 11 patients. NETs and/or Cit-H3 were observed more frequently in "the presence of bacteria in tracheal aspirate" group (11/22, 50.0%) than in "the absence of bacteria in tracheal aspirate" group (4/27, 14.8%) (p

BACKGROUND: Seroepidemiological study of parvovirus B19 has not taken place for some 20 years in Japan. To estimate the risk of parvovirus B19 infection in Japan among blood donors and pregnant women in this century, a seroepidemiological survey and statistical modeling of the force of infection were conducted. METHODOLOGY/PRINCIPAL FINDINGS: The time- and age-specific seroprevalence data were suggestive of strong age-dependency in the risk of infection. Employing a piecewise constant model, the highest forces of infection of 0.05 and 0.12 per year were observed among those aged 0-4 and 5-9 years, respectively, while estimates among older individuals were less than 0.01 per year. Analyzing the antigen detection data among blood donors, the age-specific proportion positive was highest among those aged 30-39 years, agreeing with the presence of dip in seroprevalence in this age-group. Among pregnant women, up to 107 fetal deaths and 21 hydrops fetalis were estimated to have occurred annually across Japan. CONCLUSIONS: Seroepidemiological profiles of PVB19 infection in Japan was characterized with particular emphasis on the risk of infection in blood donors and the burden of infection among pregnant women. When a vaccine becomes available in the future, a similar seroepidemiological study is expected to play a key role in planning the appropriate immunization policy.