Proactive Engagement of the Expert Meeting in Managing the Early Phase of the COVID-19 Epidemic, Japan, February-June 2020.

To deal with the risk of emerging diseases with many unknowns, close and timely collaboration and communication between science experts and policymakers are crucial to developing and implementing an effective science-based intervention strategy. The Expert Meeting, an ad hoc medical advisory body, was established in February 2020 to advise Japan's COVID-19 Response Headquarters. The group played an important role in the policymaking process, promoting timely situation awareness and developing science-based proposals on interventions that were promptly reflected in government actions. However, this expert group may have been overly proactive in taking on the government's role in crisis management. For the next stage of managing the coronavirus disease pandemic and future pandemics, the respective roles of the government and its advisory bodies need to be clearly defined. Leadership and strategic risk communication by the government are key.

Environmental Presence and Genetic Characteristics of Carbapenemase-Producing Enterobacteriaceae from Hospital Sewage and River Water in the Philippines.

This study aimed to evaluate the prevalence and genetic characteristics of carbapenemase-producing Enterobacteriaceae (CPE) in hospital sewage and river water in the Philippines, which has a typical tropical maritime climate. We collected 83 water samples from 7 hospital sewage and 10 river water sites. CPE were identified using CHROMagar mSuperCARBA, and Gram-negative strains were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) or 16S rRNA gene sequencing. Resistance genes in Enterobacteriaceae strains were identified using PCR and DNA sequencing, and transferability of carbapenemase genes from the CPE was investigated with conjugation experiments. Genotyping was performed using multilocus sequence typing (MLST) for Escherichia coli and Klebsiella pneumoniae Out of 124 Enterobacteriaceae isolates, we identified 51 strains as CPE and divided these into 7 species, 11 E. coli, 14 Klebsiella spp., 15 Enterobacter spp., and 11 others, including 4 additional species. Conjugation experiments via broth mating and using E. coli J53 revealed that 24 isolates can transfer carbapenemase-encoding plasmids. MLST analysis showed that 6 of 11 E. coli isolates belonged to clonal complex 10 (CC10). Of 11 K. pneumoniae strains, 9 unique sequence types (STs) were identified, including ST147. Five types of carbapenemase genes were identified, with the most prevalent being NDM (n = 39), which is epidemic in clinical settings in the Philippines. E. coli CC10 and K. pneumoniae ST147, which are often detected in clinical settings, were the dominant strains. In summary, our results indicate that hospital sewage and river water are contaminated by CPE strains belonging to clinically important clonal groups.IMPORTANCE Carbapenemase-producing Enterobacteriaceae (CPE) cause severe health care-associated infections, and their increasing prevalence is a serious concern. Recently, natural ecosystems have been recognized as important reservoirs of antibiotic resistance genes. We investigated the prevalence and genetic characteristics of CPE isolated from the environment (hospital sewage and river water) in the Philippines and found several CPE, including Escherichia coli and other species, with different carbapenemases. The most prevalent carbapenemase gene type was NDM, which is endemic in clinical settings. This study revealed that isolates belonging to carbapenemase-producing E. coli CC10 and K. pneumoniae sequence type 147 (ST147), which are often detected in clinical settings, were dominant in the natural environment. Our work here provides a report on the presence and characteristics of CPE in the environment in the Philippines and demonstrates that both hospital sewage and river water are contaminated by CPE strains belonging to clinically important clonal groups.

An enterohaemorrhagic Escherichia coli outbreak spread through the environment at an institute for people with intellectual disabilities in Japan in 2005.

OBJECTIVE: An enterohaemorrhagic Escherichia coli (EHEC) outbreak at an institute with multiple facilities for children and adults with intellectual disabilities was investigated to characterize the cases and identify risk factors for infection. METHODS: A case was defined as a resident, a staff member or a visitor at the institute from 16 May through 30 June 2005 testing positive for type 2 Vero toxin-producing EHEC O157:H7 (confirmed case) or exhibiting bloody diarrhoea for two or more days (probable case). We collected and analysed demographic, clinical, laboratory and individual behaviour data to identify possible risk factors for infection and infection routes. RESULTS: We recorded 58 confirmed cases, of which 13 were symptomatic. One probable case was also found. The median age of the patients was 37 years (range: 6-59 years). Thirty-six patients (61%) were male. Thirteen patients (93%) had diarrhoea and six (43%) had abdominal pain. Two developed haemolytic-uraemic syndrome but recovered. All the patients were treated with antibiotics and tested negative after treatment. Some residents had problems with personal hygiene. The residents of one of the facilities who cleaned a particular restroom had 18.0 times higher odds of being infected with EHEC (95% confidence interval: 4.0-102.4) than those who did not. DISCUSSION: The source of the outbreak could not be identified; however, the infection may have spread through environmental sources contaminated with EHEC. We recommend that institutional settings, particularly those that accommodate people with intellectual disabilities, clean restrooms as often as possible to reduce possible infection from contact with infected surfaces.

A Epidemiological Investigation of a Nosocomial Outbreak of Multidrug-Resistant Acinetobacter baumannii in a Critical Care Center in Japan, 2011-2012.

Volume 69, no. 2, p. 143-148, 2016. Page 143, Title should appear as shown below.An Epidemiological Investigation of a Nosocomial Outbreak of Multidrug-Resistant Acinetobacter baumannii in a Critical Care Center in Japan, 2011-2012.

A Epidemiological Investigation of a Nosocomial Outbreak of Multidrug-Resistant Acinetobacter baumannii in a Critical Care Center in Japan, 2011-2012.

In 2011, a multidrug-resistant Acinetobacter baumannii (MDRAB) outbreak occurred at a Japanese critical care center (CCC) in a tertiary care hospital. Multidrug-resistance in Japan is defined as resistance to the antimicrobials amikacin, carbapenem, and fluoroquinolone. We conducted a retrospective epidemiological investigation of this outbreak to identify the risk factors for MDRAB respiratory tract acquisition in this hospital. Cases were defined as hospitalized patients with MDRAB-positive cultures at least 3 days post admission to the CCC between June 1, 2011 and April 20, 2012. Fifteen MDRAB cases were identified, including 3 with infection and 12 with colonization. This case-control study demonstrated that hypoalbuminemia along with carbapenem administration were associated with MDRAB respiratory tract acquisition. Pulsed-field gel electrophoresis analysis and multilocus sequence typing using MDRAB isolates suggested a clonal dissemination of MDRAB strains with sequence type 74 occurred primarily among patients admitted to the CCC. From April 16, 2012, a decreased isolation rate of MDRAB in the hospital occurred after the implementation of the following infection control measures: closing the emergency room, discontinuing admission to the CCC, isolating patients with MDRAB colonization or infection to single room status, and conducting environmental cleaning. No MDRAB cases were detected between March 23 and April 20, 2012.

A large outbreak of enterohaemorrhagic Escherichia coli O157, caused by low-salt pickled Napa cabbage in nursing homes, Japan, 2012.

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.

Microbiological and molecular epidemiological analyses of community-associated methicillin-resistant Staphylococcus aureus at a tertiary care hospital in Japan.

Molecular characterization of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is generally conducted referred to staphylococcal cassette chromosome mec (SCCmec) type IV or V. CA-MRSA is now a cause of concern since such strains have been isolated not only from individuals in a community but also from patients in healthcare settings. The aim of this study was to analyze microbiological and molecular epidemiological features of CA-MRSA strains at a Japanese tertiary care hospital using PCR based-open reading frame typing (POT). This technique allows for molecular classification into CA-MRSA (POT-CA) and hospital-associated (HA-) MRSA (POT-HA) with clonal discrimination. Clinical MRSA isolates obtained from consecutive patients between October 1, 2012 and September 30, 2013 at the hospital were analyzed in combination with the clinical definition for CA-MRSA by the Centers for Disease Control and Prevention and POT. Of 219 isolates (76 clonal groups), 64 (29.3%) were clinical-HA/POT-CA isolates (22 clonal groups). Some clones of them accumulated in this hospital and might be involved in nosocomial transmission. Virulent factors of the isolates were analyzed, and only one (1.6%) Panton-Valentine leukocidin gene positive isolate but no arginine catabolic mobile element genes positive isolate were found in clinical-HA/POT-CA. Additionally, clinical-HA/POT-CA isolates showed higher antimicrobial susceptibility than clinical-HA/POT-HA, especially to minocycline, doxycycline, and amikacin. The most frequent genotype of molecular CA-MRSA was multi-locus sequence type 5-SCCmecIV, previously not detected in Japan. Although CA-MRSA at this hospital showed low virulence and higher antimicrobial susceptibility, the risk of nosocomial infection from them should be recognized, requiring stricter infection control measures.

A large outbreak of enterohaemorrhagic Escherichia coli O157, caused by low-salt pickled Napa cabbage in nursing homes, Japan, 2012

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.

[Adverse events during pemetrexed administration caused by concomitant nonsteroid anti-inflammatory therapy].

Pemetrexed, a folate metabolic antagonist, is considered to be effective against plural mesotheliomas, non-small cell lung cancer, and especially for non-squamous cell cancer. However, it has been reported to have adverse interactions with nonsteroid anti-inflammatory drugs(NSAIDs). In the present study, we compared the incidence of adverse events between patients receiving pemetrexed therapy with and without concomitant NSAID administration. No significant difference in the incidence of hematotoxic events of Grade 3 or worse was observed. As for the incidence of non-hematotoxic events, the increase in the amount of creatinine, namely a severe adverse effect of Grade 2 or more, was significantly higher in the combined therapy group (p=0.018). No other significant differences were noted for other adverse events. A creatinine increase to Grade 2 or greater developed significantly earlier in the combined group(median value, 12.7 courses; p=0.0063). Our results suggest that renal dysfunction may easily develop as a result of continued pemetrexed administration combined with NSAID therapy. Therefore, it is necessary to take precautions against adverse side effects such as renal dysfunction when combining pemetrexed with NSAID therapy, by conducting periodic examinations.

Epidemiological and genetic analyses of a diffuse outbreak of hepatitis A in Japan, 2010.

BACKGROUND: Hepatitis A virus (HAV) is still one of the most common causative agents of acute hepatitis in Japan. Although a relatively small number of annual acute hepatitis A cases (approximately 100-150, 0.78-1.17 per million) were recently reported, a larger number of cases (346, 2.71 per million) were reported in 2010. OBJECTIVES: To investigate the causes of the 2010 HAV resurgence in Japan by using molecular epidemiological and genetic analyses. STUDY DESIGN: HAV specimens were obtained from 61 cases from 22 different prefectures. These viral specimens were genotyped by PCR amplification and sequencing of the VP1/2A region of HAV genome. RESULTS: Phylogenetic analysis revealed that 61 HAV strains could be divided into three genotypes: IA (44 cases), IB (1 case) and IIIA (16 cases). The IA genotype consisted of two genomic sub-lineages. The sequences of one of the two IA sub-lineages (corresponding to 31 cases) were very similar, 26 of these 31 isolates had 100% identity. The other IA sub-lineage corresponded to strains endemic to Japan. The sequences of Japanese IIIA strains were similar to those of strains that caused a large epidemic in the Republic of Korea from 2007 to 2009. CONCLUSIONS: The resurgence of HAV in 2010 can be attributed to importation of two newly emerged HAV genotypes.

[Global surveillance and the disease pandemics].

Humans experienced various disease pandemics in the history of the world. Disease can spread over the world more rapidly and in larger scale than in any other time in the past as the world is getting smaller. The World Health Organization established its innovative event-based surveillance system in close collaboration with many partners at global scale for early detection and rapid response to the public health events (PHE) of international importance in 1997. It has been being strengthened to respond effectively to PHEs in harmony with the International Health Regulations which were revised in 2005.

Risk factors for severe hand foot and mouth disease.

BACKGROUND: Hand foot and mouth disease (HFMD) and herpangina are enteroviral infectious diseases caused mainly by Coxsackie virus A (CA) or enterovirus 71 (EV71). From 2000 to 2002, many complicated cases were reported in Japan, therefore a nationwide questionnaire survey was carried out to assess the situation. The subjects were patients with HFMD or herpangina, or other enterovirus infection from 2000 to 2002, who were either hospitalized over 24 h or who died. The response rates were 41.3% in 2000 and 2001 and 31.6% in 2002. The survey period included the year 2000, when HFMD epidemics due to EV71 occurred. To examine risk factors causing complications of enterovirus infection, severe cases of HFMD were focused on. METHODS: HFMD cases in 2000 were divided into two groups according to severity: 'more severe' and 'less severe'. 'More severe' was defined as 'fatal, involving sequelae, or involving hospitalization for 7 days or longer'. Statistical analyses were conducted with Epi info version 3.3 and the association between risk factors and severity was estimated. RESULTS: The number of patients with more severe and less severe cases was 96 and 103, respectively. There was no difference in sex, age, having siblings and family history between the two groups. There was a significant association between attending child care center and severe HFMD. CONCLUSIONS: It is not clear why attending child care centers was associated with HFMD severity. Further study is needed.

[A high school measles outbreak--control measures and vaccine efficacy].

Epidemiological investigation of a March 2007 detected measles outbreak of 28 cases in a 792-student high school in Tokyo. Students with a vaccination history had significantly milder symptoms than those without, and no cases occurred among students having two of measles vaccine in two doses of measles vaccine in their childhood. Vaccine efficacy (VE) calculated in our investigation was 93.9% (95% CI:87-97), and no significant difference was observed in vaccine type or manufacturer product. Students and parents were extremely difficult to persuade to cooperate in control measures such as emergency vaccination and home isolation through notification letters even during outbreaks. Schools should thus develop measles outbreak preparedness and response plans and identify potentially susceptible students in advance through documented proof of case histories and MCV vaccination. Outbreaks should promote early detection of patients and emergency vaccination targetting potentially susceptible students backed through close cooperation with medical facilities, education institutions, and the public health sector, together with school closures as appropriate.

Serological survey of avian H5N2-subtype influenza virus infections in human populations.

To investigate the distribution of antibodies against H5N2 influenza virus in humans living in Ibaraki prefecture, Japan, 266 single serum samples were collected to perform serological tests. Results were compared to investigate the relationship between positive results and several factors. The number of positive serum neutralization antibody titers (> or = 40) against avian influenza virus A/H5N2 was significantly greater (P < 0.05) among poultry workers, in comparison to a Japanese healthy population. The geometric mean titers of serum neutralization antibody against A/H5N2 were significantly higher (P < 0.05) among Ibaraki inhabitants and poultry workers (P < 0.0001) when compared to a Japanese healthy population. Seropositivity against A/H5N2 virus was significantly (P < 0.05) associated with age (> or = 50 years old) in poultry workers. These results suggest that seropositivity against H5N2 virus in Ibaraki specimens is significantly higher than those of a Japanese healthy population and that the surveillance of avian influenza viruses is very important to evaluate the invasion or emergence of new pandemic influenza viruses from species other than humans.

Human H5N2 avian influenza infection in Japan and the factors associated with high H5N2-neutralizing antibody titer.

BACKGROUND: H5N2 avian influenza virus infection of humans has not been reported thus far. The first H5N2 avian influenza infection of poultry in Japan occurred in Ibaraki. METHODS: The subjects were workers at 35 chicken farms in Ibaraki Prefecture, where the H5N2 virus or antibody was isolated from chickens. None of the subjects exhibited influenza symptoms. The H5N2-neutralizing antibody titers of the first and second paired sera samples were compared. To investigate the possible factors for this increase, the H5N2-neutralizing antibody titer (1:40 or more) was calculated for the second samples. A logistic regression analysis was performed to examine the association of these factors with H5N2-neutralizing antibody positivity. RESULTS: We performed Wilcoxon matched-pairs signed-ranked test on data collected from 257 subjects, and determined that the H5N2 antibody titers of the second paired sera samples were significantly higher than those of the first samples (P < 0.001). The H5N2 antibody titers of paired sera of 13 subjects without a history of seasonal influenza vaccination within the previous 12 months increased 4-fold or more. The percentage of antibody positivity was 32% for subjects with a history of seasonal influenza vaccination (28% of all subjects) and 13% for those without a history of the same. The adjusted odds ratio of H5N2-neutralizing antibody positivity was 4.6 (95% confidence interval: 1.6-13.7) for those aged over 40 and 3.1 (95% confidence interval: 1.6-6.1) for those with a history of seasonal influenza vaccination within the previous 12 months. CONCLUSION: The results suggest that this may have been the first avian influenza H5N2 infection of poultry to affect humans. A history of seasonal influenza vaccination might be associated with H5N2-neutralizing antibody positivity.