[Recent Trends in Infection and Related Examinations: Infectious Diseases and Their Control in Other Countries (General Remarks)].

In a borderless era, infectious diseases that are prevalent in other countries may also spread to Japan at any time. Among such diseases, attention should particularly be paid to emerging, re-emerging, and zoonosis, arthropod-borne infectious diseases, as well as those occurring after major disasters. Important emerging infectious diseases include SARS, swine influenza, MERS, and infection by antimicrobial-resistant bacteria, while zoonosis is represented by rabies. Rabies is a vaccine-preventable, but vaccination is insufficient due to high costs in some areas. Arthropod-borne infectious diseases, such as malaria, dengue fever, Chikungu- nya fever, Zika fever, and yellow fever, are also important. Learning various lessens from the management of these diseases in other countries, human resource development is currently being promoted in Japan. [Review].

Association of severe COVID-19 outcomes with radiological scoring and cardiomegaly: findings from the COVID-19 inpatients database, Japan.

PURPOSE: We aimed to characterize novel coronavirus infections based on imaging [chest X-ray and chest computed tomography (CT)] at the time of admission. MATERIALS AND METHODS: We extracted data from 396 patients with laboratory-confirmed COVID-19 who were managed at 68 hospitals in Japan from January 25 to September 2, 2020. Case patients were categorized as severe (death or treatment with invasive ventilation during hospitalization) and non-severe groups. The imaging findings of the groups were compared by calculating odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for sex, age, and hospital size (and radiographic patient positioning for cardiomegaly). Chest X-ray and CT scores ranged from 0 to 72 and 0 to 20, respectively. Optimal cut-off values for these scores were determined by a receiver-operating characteristic (ROC) curve analysis. RESULTS: The median age of the 396 patients was 48 years (interquartile range 28-65) and 211 (53.3%) patients were male. Thirty-two severe cases were compared to 364 non-severe cases. At the time of admission, abnormal lesions on chest X-ray and CT were mainly observed in the lower zone/lobe. Among severe cases, abnormal lesions were also seen in the upper zone/lobe. After adjustment, the total chest X-ray and CT score values showed a dose-dependent association with severe disease. For chest X-ray scores, the area under the ROC curve (AUC) was 0.91 (95% CI = 0.86-0.97) and an optimal cut-off value of 9 points predicted severe disease with 83.3% sensitivity and 84.7% specificity. For chest CT scores, the AUC was 0.94 (95% CI = 0.89-0.98) and an optimal cut-off value of 11 points predicted severe disease with 90.9% sensitivity and 82.2% specificity. Cardiomegaly was strongly associated with severe disease [adjusted OR = 24.6 (95% CI = 3.7-166.0)]. CONCLUSION: Chest CT and X-ray scores and the identification of cardiomegaly could be useful for classifying severe COVID-19 on admission.

Airport quarantine inspection, follow-up observation, and the prevention of pandemic influenza.

INTRODUCTION: After a report of H1N1 novel influenza in Mexico and North America, Japan conducted onboard quarantine inspections from late April 2009. The detection rate in border quarantine inspection is low due to incubation period and thus inspection is considered to be ineffective in blocking the entry of influenza. However, little is known about the concomitant effects of such inspection, such as increased traceability, upon secondary transmission. METHODS: Epidemiological data were collected from the web sites of the Department of Health, Labor, and Welfare of Japan and the National Institute of Infectious Diseases of Japan. The number of weekly patients with H1N1 pandemic influenza in eight districts of Japan was summarized. The number of patients who passed through quarantine inspection at the airports was also calculated. A person with overseas travel history was defined as a person who had a flight only from the United States, Canada, or Mexico and passed through the quarantine inspection (according to the quarantine policy of the Japanese government). The numbers were adjusted for the population of each district and expressed as the number of patients per one million people. RESULTS: Despite Kanto district having the largest population, the number of patients with H1N1 novel influenza was relatively small. The total number of cases in each district correlated inversely to the percentage of cases with airport quarantine inspection. DISCUSSION: Quarantine inspection at the airports, follow-up observation by local authorities, and overall concomitant efforts may have contributed to secondary infection control in Japan.

[Field epidemiology investigation on measles outbreak started from a junior high school at Kita Ibaraki City].

We studied measles outbreak in Ibaraki Prefecture in spring 2002 as members of Field Epidemiology Training Program Japan (FETPJ). Of 84 cases diagnosed by not laboratory test but clinically, 67 (79.8%) were junior high school students, 9 (10.7%) were other students, and 8 (9.5%) were ordinary adult and infant citizens. Of the 84, 46 (54.8%) had been vaccinated. Most did not show typical Koplik spots. The city in which the school was located promoted vaccinations for infants and children aged 7.5 years old to grade 1 in High school. Questionnaire given to junior high students were detected 86 cases, of whom 57 (66.3%) were male. Overall, 4 peaks of clusters were observed in an epidemic curve, among which graduates' farewell parties and graduation ceremonies were the most common opportunities for measles virus exposure. The overall vaccination rate at school was 82.2%, vaccine efficacy extremely low at 72.5%, and vaccine failure high at 15.2%. Symptoms among those vaccinated were significantly milder than those not vaccinated. Immunity of those vaccinated as infants may have been decreased due to scarcity of measles cases in the last 10 years. In such situations--much less in typical measles among susceptible non affected and non vaccinated subjects--atypical or mild measles may be difficult to diagnose. These findings may keep clarify the need to introduce two-dose measles immunization in Japan.

Carriage Rate and Characteristics of Neisseria meningitidis among Dormitory Students.

In Japan, several meningococcal disease outbreaks have recently been reported among adolescent dormitory residents of schools. However, little is known about meningococcal carriage dynamics in healthy individuals. The purpose of this study was to investigate the carriage rate over time and characteristics of Neisseria meningitidis strains among dormitory students. The survey was conducted twice between November 2018 and January 2019 for first- to third-year students (N = 376) in a medical school dormitory. The two surveys yielded carriage rates of 0.4% (one positive among 257 students) and 2.1% (two positives among 97 students, including 90 re-participants). No transmission or persistence of a specific strain was observed during the two months. A limited number of students had a history of potential risk behaviors for carriage, such as smoking (3.0% [6/202] aged ≥20 years and 5.2% [4/77] aged ≥20 years, respectively) and attending parties more than once a week (4.3% [11/257] and 2.1% [2/97], respectively). Two isolates were unencapsulated, consistent with asymptomatic participants.

Medicine at mass gatherings: current progress of preparedness of emergency medical services and disaster medical response during 2020 Tokyo Olympic and Paralympic Games from the perspective of the Academic Consortium (AC2020).

Mass gatherings are events characterized by "the concentration of people at a specific location for a specific purpose over a set period of time that have the potential to strain the planning and response resources of the host country or community." Previous reports showed that, as a result of the concentration of people in the limited area, injury and illness occurred due to several factors. The response plan should aim to provide timely medical care to the patients and to reduce the burden on emergency hospitals, and to maintain a daily emergency medical services system for residents of the local area. Although a mass gathering event will place a significant burden on the local health-care system, it can provide the opportunity for long-term benefits of public health-care and improvement of daily medical service systems after the end of the event. The next Olympic and Paralympic Games will be held in Tokyo, during which mass gatherings will occur on a daily basis in the context of the coronavirus disease (COVID-19) epidemic. The Academic Consortium on Emergency Medical Services and Disaster Medical Response Plan during the Tokyo Olympic and Paralympic Games in 2020 (AC2020) was launched 2016, consisting of 28 academic societies in Japan, it has released statements based on assessments of medical risk and publishing guidelines and manuals on its website. This paper outlines the issues and countermeasures for emergency and disaster medical care related to the holding of this big event, focusing on the activities of the academic consortium.

Measurement of (1-3)-beta-D-glucan derived from different gauze types.

(1-3)-beta-D-glucan (BDG) is a cell-wall polysaccharide component found in most fungi. The measurement of BDG is a useful diagnostic marker for invasive fungal infections. However, it is well known that interfering substances can result in false positive reactions. We encountered a patient who underwent lung transplantation and presented with highly elevated BDG values, despite having no evidence of invasive fungal infection. We therefore hypothesized that elevated BDG values were originated from the gauze products used during surgery. While it is known that gauze products contain BDG, there have been no previous reports to quantitatively correlate amount of gauze usage and BDG levels. In this study, we extracted BDG from various gauze products and measured BDG to better understand the degree of which gauze contributes to elevated BDG values. Six types of commonly used surgical gauze products were selected for our study. Each of the surgical gauze was immersed in sterile, purified water for up to 120 minutes. At set intervals, BDG values in the water extracts were measured. Purified water samples without gauze were used as negative controls (< 4 pg/ml). After 120-minute extraction, BDG levels varied greatly depending on gauze products, ranging from 11.7 pg/ml to 6612 pg/ml. The gauze made of lyocell, which is a fiber produced from wood pulp cellulose, yielded the lowest levels of BDG, and probably would not cause false positive for fungal infections. There is a need for the development of a gauze product that does not contribute to elevated BDG values.

Characterization of a novel thogotovirus isolated from Amblyomma testudinarium ticks in Ehime, Japan: A significant phylogenetic relationship to Bourbon virus.

The genus Thogotovirus, as represented by Thogoto virus and Dhori virus, comprises a group of arthropod-borne viruses, most members of which are transmitted by ticks. Here we report the genetic and biological characterization of a new thogotovirus, designated Oz virus (OZV), isolated from the hard tick Amblyomma testudinarium in Ehime, Japan. OZV efficiently replicated and induced a cytopathic effect in Vero cells, from which enveloped pleomorphic virus particles were formed by budding. OZV could also replicate in BHK-21 and DH82 cells and caused high mortality in suckling mice after intracerebral inoculation. Phylogenetic analyses of six viral proteins indicated that OZV is clustered with Dhori and related viruses, and is most closely related in glycoprotein (GP) and matrix protein (M) sequences to Bourbon virus, a human-pathogenic thogotovirus discovered recently in the United States. Our findings emphasize the need for understanding the geographic distribution and ecology of OZV and related viruses and for reevaluation of the medical and public health importance of thogotoviruses.

Isolation and characterization of Kabuto Mountain virus, a new tick-borne phlebovirus from Haemaphysalis flava ticks in Japan.

In Japan, indigenous tick-borne phleboviruses (TBPVs) and their associated diseases first became evident in 2013 by reported human cases of severe fever with thrombocytopenia syndrome (SFTS). In this study, we report a novel member of the genus Phlebovirus designated as Kabuto Mountain virus (KAMV), which was isolated from the ixodid tick Haemaphysalis flava in Hyogo, Japan. A complete viral genome sequencing and phylogenetic analyses showed that KAMV is a novel member of TBPVs, which is closely related to the Uukuniemi and Kaisodi group viruses. However, unlike the Uukuniemi group viruses, the 165-nt intergenic region (IGR) in the KAMV S segment was highly C-rich in the genomic sense and not predicted to form a secondary structure, which are rather similar to those of the Kaisodi group viruses and most mosquito/sandfly-borne phleboviruses. Furthermore, the NSs protein of KAMV was highly divergent from those of other TBPVs. These results provided further insights into the genetic diversity and evolutionary relationships of TBPVs. KAMV could infect and replicate in some rodent and primate cell lines. We evaluated the infectivity and pathogenicity of KAMV in suckling mice, where we obtained a virulent strain after two passages via intracerebral inoculation. This is the first report showing the existence of a previously unrecognized TBPV in Japan, other than the SFTS virus.

Malaria and mefloquine prophylaxis use among Japan Ground Self-Defense Force personnel deployed in East Timor.

BACKGROUND: Malaria poses a significant threat to military personnel stationed in endemic areas; therefore, it is important to examine the risks of military operations, particularly in areas where malaria-related data are scarce. The recent deployment of Japan Ground Self-Defense Force (JGSDF) for a peacekeeping operation in East Timor provided an opportunity to investigate these risks. The results of these studies may be translated into chemoprophylactic strategies for travelers. METHODS: A total of 1,876 members were deployed between April 2002 and September 2003. They consisted of three battalions; each remained for 6 months and was put on mefloquine prophylaxis. Malaria infection was investigated, including exposure to Plasmodium falciparum sporozoites, assessed by seroconversion for anticircumsporozoite (anti-CS) protein antibodies. Adherence to and adverse events (AEs) of mefloquine were studied via questionnaires. RESULTS: Four members were evacuated: one each with optic neuritis, lung cancer with brain metastasis, IgA nephropathy, and psychotic reactions that may have been precipitated by mefloquine. Six clinical episodes of Plasmodium vivax occurred, including one relapse, but there were no clinical cases of P falciparum, yielding a crude malaria attack rate of 0.32% for the 6-month period. Overall, 3.1% of the study population seroconverted for the anti-CS protein antibodies, with some regional differences noted. About 24% of questionnaire respondents, reported AEs; however, none of the AEs was severe. The AEs tended to emerge during the initial doses of chemoprophylaxis. CONCLUSIONS: The implementation of mefloquine prophylaxis among JGSDF personnel in East Timor, where P falciparum constitutes a moderate risk, appears to have been a success. Mefloquine prophylaxis was generally safe for Japanese unless predisposed to neuropsychiatric illness. However, given that mefloquine is the only chemoprophylactic agent available, a risk-benefit analysis tailored to the traveler is required for visits to countries such as East Timor.

Epidemiology of Imported Malaria Cases in Japan, 2006-2014: A Sentinel Traveler Surveillance Approach.

Malaria continues to be imported into Japan. To better assess the risk of imported malaria, we describe malaria species, suspected country/area of infection (accounting for the number of travelers), demographic characteristics, clinical manifestation, and healthcare access, based on the national surveillance data from 2006 to 2014. Among 557 cases, the median age was 33 years (range: 1-83 years), and 76% were male; 306 (55%) were classified as Japanese based on the reported name. The majority were Plasmodium falciparum infections (58%), followed by Plasmodium vivax infections (30%). Most P. falciparum cases were acquired in Africa and P. vivax in Asia/Oceania. Notification rates per 10,000 Japanese travelers for P. falciparum were highest for Africa, P. vivax were highest for Asia/Oceania, and high for both species for Papua New Guinea. Ten percent of the cases were clinically severe at the time of notification. Nearly 80% of severe cases were P. falciparum infections, and among P. falciparum cases, Japanese ethnicity was associated with severe case status (P = 0.03). Plasmodium falciparum cases among Japanese cases showed that older age (≥ 50 years) was associated with severe case status (odds ratio = 5.4; 95% confidence interval = 1.9-15.2), adjusted for sex and healthcare access. More informative assessments are possible by accounting for the number of travelers. Older Japanese represent an important demographic to target prevention and early treatment efforts for malaria.

Chikungunya Fever in Japan Imported from the Caribbean Islands.

A 53-year-old Japanese woman who was working as a volunteer in the Commonwealth of Dominica in the Caribbean islands presented with a high-grade fever and severe incapacitating generalized arthralgia. The Asian genotype of the chikungunya virus was confirmed using reverse transcription-PCR and serology, based on the presence of a specific neutralization titer and immunoglobulin M antibodies. She was diagnosed with post-chikungunya chronic arthritis based on persistence of her polyarthritis for 3 months and the presence of rheumatoid factor, immunoglobulin G-rheumatoid factor, and matrix metalloproteinase-3. Chikungunya virus should be considered as a causative pathogen in travelers returning from Caribbean islands. Clinicians should consider chikungunya fever in the differential diagnosis of patients who complain of chronic arthritis and have a history of travel to an endemic area.

[An estimation of imported infections concerning 2002 FIFA world cup Korea/Japan].

The FIFA World Cup 2002 Korea/Japan, which will be held during May 31 through June 30, 2002, is a mass-gathering and high-profile event. The Ministry of Transport announced that approximately 430,000 people visit Japan for the event. We estimated the incidence of major imported infections using data from the national epidemiological surveillance of infectious diseases and the statistics of immigration. Estimated incidences are 5.88 (shigellosis), 3.41 (malaria), 1.40 (typhoid/paratyphoid fever), 0.42 (cholera), and 0.0032 (meningococcal meningitis). The incidence for viral hemorrhagic fever was estimated 0.0018 under assumption that "it correlates with the malaria incidence from Africa" and that "the incidence occurs every 15 years". These results indicate little possibility of remarkable increase of exotic infections during the event. These incidences, however, may occur in the rural prefectures where few cases are reported. It is highly needed to strengthen surveillance and educate physicians and public health experts especially for malaria cases.

[An evaluation of syndromic surveillance for the G8 Summit in Miyazaki and Fukuoka, 2000].

Syndromic surveillance was performed during the G8 Summit held in Fukuoka and Miyazaki City in July 2000. Any case suspected as acute infectious disease was reported from designated medical facilities. Those cases were categorized in 5 clusters including "hemorrhagic and skin symptoms", "respiratory symptoms", "gastroenteric symptoms", "neural symptoms", and "miscellaneous symptoms". To compare how closely these incidence trends were representing those of the infectious disease surveillance, these results were analyzed for two weeks. In Miyazaki, duplicated report were accepted when more than one symptom were found. The ratio of weekly reported number for each cluster was calculated for two weeks, and then the ratio for former/latter week was calculated for each cluster. The results from Fukuoka and Miyazaki surveillance revealed the average former/latter ratio +/- SD = 0.99 +/- 0.292, 95% CI; 0.71-1.28 and 1.19 +/- 0.298, 0.93-1.45, respectively. These results indicate that syndromic surveillance is well represented with the infectious disease surveillance trends. Single reporting, employed in Fukuoka, was easier for analysis. Reported number for acute respiratory syndrome was larger than that of infectious disease surveillance, indicating that the latter could not detect non-reportable adult cases. Syndromic surveillance enables us to show the trend quickly and it can be carried out with smaller costs and human resources. This study concluded that a syndromic surveillance is effective for such high-profile events, but sometimes it is hard to analyze the trend accurately, because of insufficient period of baseline data, number and size of the reporting sentinel facilities.

[A comparative analysis of zoonosis and vector surveillance systems].

PURPOSE: To investigate zoonosis and vector surveillance systems in major countries, conducted by quarantine, health and environment authorities, and compare the results with the current Japanese systems. METHODS: We elaborated a questionnaire for zoonosis and vector surveillance systems regarding target diseases, vectors, period and area of operation, type of surveillance (active and/or positive), and feedback mechanisms which was then mailed to ten countries having strong trade and tourism links with Japan. We visited some authorities for further discussions. RESULTS: Eight countries which responded answered that all were conducting zoonosis and vector surveillance. Target diseases included those designated by the International Health Regulations and others with a higher priority for control and prevention in the individual countries. The type of surveillance was classified as: regular monitoring of the vector population, active detection of pathogens in vectors during a specific time period of a year, and intensive pathogen characterization when problems occurred. CONCLUSIONS: The significance of zoonosis and vector surveillance was recognized through this investigation, where we found differences in target diseases, and type of operation. The results should be utilized for generation of more useful and efficient surveillance systems in Japan.

Trial to control an outbreak of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus at a boarding school in Japan.

BACKGROUND: Our retrospective investigation of methicillin-resistant Staphylococcus aureus (MRSA) infection at a hospital in Japan around 2007 suggested dissemination of community-associated MRSA (CA-MRSA) strains among healthy students in a Japanese boarding school, which frequently caused skin disease and exhibited the same antibiogram patterns. METHODS: Active surveillance of skin diseases for 6 months after May 2008, examination of MRSA carriage in selected high-risk groups, and investigation of their life circumstances, including environmental cultures, were conducted in the school. Furthermore, we strengthened hygiene practices and improved recognized risk factors from November 2008 and observed the occurrence of skin diseases and MRSA carriage rate for the evaluation of infection controls. RESULTS: We identified 21 patients with skin diseases in whom MRSA strains were isolated. MRSA colonization rates in 3 selected groups ranged from 7.6% to 36.6%. The rates of both skin disease and MRSA carriage decreased significantly after infection controls were introduced. Genetic analysis revealed a main dissemination of a PVL-positive SCCmec IVc clone (41/47 isolates in total), presenting as a different pulsed-field type than USA300. CONCLUSION: This first report of a PVL-positive CA-MRSA outbreak in Japan demonstrates systematic management of dissemination by conducting surveillance in a closed community.