[Biorisk Management for Clinical Diagnostic Laboratories].

The mission of the clinical diagnostic laboratory is to continuously provide high-quality diagnostic services. For this purpose, quality management, continuous technical improvement, work place safety assurance, and biosecurity are their objectives. Biorisks arise from handling clinical samples categorized at the highest risk level due to their unknown nature. The "undetermined risk" was not able to risk assess by predetermined risk management approach explained in many existing biosafety references, such as the Biosafety in Microbi- ological and Biomedical Laboratories. By reviewing books, documents, article, and standard guidelines on biorisk management or biosafety, this report provides a comprehensive summary of how biorisk is defined, the existing approach to biorisk assessment, how human factors play roles in biorisk assessment, how vital communication and incident reporting are in biorisk management, and how the biorisk management system support the clinical diagnostic laboratories to fulfil their mission. Given that laboratories are already imple- menting the Quality Management System from the International Standard Organization and starting to report its positive impact on daily activity, it is logical to consider how to integrate the biorisk management system together. A biorisk management system will allow a laboratory to continue business at a high standard not just by preventing laboratory accidents, but proactively reducing near misses and incidents and improving diagnostic process efficiency through risk-assessment-based biosafety and biosecurity. [Review].

Latitude-based approach for detecting aberrations of hand, foot, and mouth disease epidemics.

BACKGROUND: Epidemics of hand, foot and mouth disease (HFMD) among children in East Asia have been a serious annual public health problem. Previous studies in China and island-type territories in East Asia showed that the onset of HFMD epidemics evolved with increased latitude. Based on the natural characteristics of the epidemics, we developed regression models for issuing aberration alerts and predictions. METHODS: HFMD sentinel surveillance data from 2008 to 2014 in Japan are used in this study, covering 365 weeks and 47 prefectures between 24 and 46° of north latitude. Average HFMD cases per sentinel are standardized as Z rates. We fit weekly Z rate differences between prefectures located in the south and north of a designated prefecture with linear regression models to detect the surging trend of the epidemic for the prefecture. We propose a rule for issuing an aberration alert determined by the strength of the upward trend of south-north Z rate differences in the previous few weeks. In addition to the warning, we predict a Z rate for the next week with a 95% confidence interval. RESULTS: We selected Tokyo and Kyoto for evaluating the proposed approach to aberration detection. Overall, the peaks of epidemics in Tokyo mostly occurred in weeks 28-31, later than in Kyoto, where the disease peaked in weeks 26-31. Positive south-north Z rate differences in both prefectures were clearly observed ahead of the HFMD epidemic cycles. Aberrations in the major epidemics of 2011 and 2013 were successfully detected weeks earlier. The prediction also provided accurate estimates of the epidemic's trends. CONCLUSIONS: We have used only the latitude, one geographical feature affecting the spatiotemporal distribution of HFMD, to develop rules for early aberration detection and prediction. We have also demonstrated that the proposed rules performed well using real data in terms of accuracy and timeliness. Although our approach may provide helpful information for controlling epidemics and minimizing the impact of diseases, the performance could be further improved by including other influential meteorological factors in the proposed latitude-based approach, which is worth further investigation.

Number of sentinel medical institutions needed for estimating prefectural incidence in influenza surveillance in Japan.

BACKGROUND: The sentinel surveillance system in Japan provides estimates of nationwide influenza incidence. Although prefectural influenza incidences can be estimated using data from the current surveillance system, such estimates may be imprecise. METHODS: We calculated the numbers of sentinel medical institutions (SMIs) needed in the surveillance system to estimate influenza incidences in prefectures, under the assumption that the standard error rates in 75% of influenza epidemic cases are less than 10%. Epidemic cases observed in 47 prefectures during the 2007/2008, 2008/2009, and 2009/2010 seasons, respectively, were used. RESULTS: The present total number of SMIs was 6669. With respect to current standards, the increases required in prefectures ranged from 0 to 59, and the total increase required in the number of SMIs was 1668. CONCLUSIONS: We used sentinel surveillance data for Japan to calculate the number of SMIs required to estimate influenza incidence in each prefecture.

Clinical factors associated with severity in hospitalized children infected with avian influenza (H5N1).

OBJECTIVE: The World Health organization received reports of 478 laboratory-confirmed cases of influenza A (H5N1) from 15 countries between November 2003 and February 2010. More than 50% of these cases involved patients <20 years of age. Determining an association between the clinical factors at the time of hospital admission and prognosis may be useful for timely and adequate consultation and treatment. It has been difficult to obtain these clinical factors adjusted with other confounding factors, such as age and sex, as published studies of H5N1 virus infection usually reported only a few cases. So, we performed a pooled analysis of the reported cases. METHODS: Five case reports (36 patients <18 years of age) of H5N1 infection from four countries published between 2004 and 2009 were assessed based on available individual clinical data. Using the pooled data for all patients, we investigated the associations between patients' prognosis and available laboratory findings, such as white blood cell (WBC) counts, platelet (PLT) counts, and serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) by adjusting for age and/or sex. RESULTS: The linear regression analysis revealed that mortality was negatively associated with WBC and PLT counts adjusted with age and sex. Increased log AST tended to be associated with a poor prognosis (p = 0.054), but there was no significant association between survival and log ALT level. CONCLUSIONS: Both decreased WBC and PLT counts can be considered to be common predictors of poor prognosis in H5N1 influenza patients <18 years of age. Further studies are needed for clarification.

Descriptive epidemiology of rickettsial infections in Japan: Scrub typhus and Japanese spotted fever, 2007-2016.

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.

BioCaster: detecting public health rumors with a Web-based text mining system.

SUMMARY: BioCaster is an ontology-based text mining system for detecting and tracking the distribution of infectious disease outbreaks from linguistic signals on the Web. The system continuously analyzes documents reported from over 1700 RSS feeds, classifies them for topical relevance and plots them onto a Google map using geocoded information. The background knowledge for bridging the gap between Layman's terms and formal-coding systems is contained in the freely available BioCaster ontology which includes information in eight languages focused on the epidemiological role of pathogens as well as geographical locations with their latitudes/longitudes. The system consists of four main stages: topic classification, named entity recognition (NER), disease/location detection and event recognition. Higher order event analysis is used to detect more precisely specified warning signals that can then be notified to registered users via email alerts. Evaluation of the system for topic recognition and entity identification is conducted on a gold standard corpus of annotated news articles. AVAILABILITY: The BioCaster map and ontology are freely available via a web portal at http://www.biocaster.org.

Structuring an event ontology for disease outbreak detection.

BACKGROUND: This paper describes the design of an event ontology being developed for application in the machine understanding of infectious disease-related events reported in natural language text. This event ontology is designed to support timely detection of disease outbreaks and rapid judgment of their alerting status by 1) bridging a gap between layman's language used in disease outbreak reports and public health experts' deep knowledge, and 2) making multi-lingual information available. CONSTRUCTION AND CONTENT: This event ontology integrates a model of experts' knowledge for disease surveillance, and at the same time sets of linguistic expressions which denote disease-related events, and formal definitions of events. In this ontology, rather general event classes, which are suitable for application to language-oriented tasks such as recognition of event expressions, are placed on the upper-level, and more specific events of the experts' interest are in the lower level. Each class is related to other classes which represent participants of events, and linked with multi-lingual synonym sets and axioms. CONCLUSIONS: We consider that the design of the event ontology and the methodology introduced in this paper are applicable to other domains which require integration of natural language information and machine support for experts to assess them. The first version of the ontology, with about 40 concepts, will be available in March 2008.

Quantitative modeling for risk assessment of Vibrio parahaemolyticus in bloody clams in southern Thailand.

A risk assessment of Vibrio parahaemolyticus in bloody clams (Anadara granosa) consumed in southern Thailand was conducted. This study estimated the prevalence and concentration of pathogenic V. parahaemolyticus in bloody clams at harvest and retail stages; and during this process, methods to detect the total and pathogenic V. parahaemolyticus were investigated. Consumption of bloody clams and cooking efficiency were studied using interviews and on-site observation of consumers. A beta-Poisson dose-response model was used to estimate probability of illness applying estimation methods for the most likely parameter values presented by USFDA. Microbial and behavioral data were analyzed by developing a stochastic model and the simulation gave a mean number of times a person would get ill with V. parahaemolyticus by consuming bloody clams at 5.6 x 10(-4)/person/year. Sensitivity analysis demonstrated the fraction of people who did not boil the clams properly was the primary factor in increasing risk. This study serves as an example of how a microbiological risk assessment with limited data collection and international cooperation leads to valuable local insight.

[An experimental study for syndromic surveillance using OTC sales].

OBJECTIVES: We analyzed the possibility of using sales data on over-the-counter (OTC) medicine in syndromic surveillance for early detection and/or prediction of influenza pandemics. METHODS: Data who collected on daily November 2003-April 2004 sales of common cold medication commercially obtained from 600 pharmacies in Japan enrolled in reporting throughout the 2003/04 influenza season. OTC sales data were compared to daily influenza incidence data to determine correlations and predictability. Data included Sentinel Surveillance of influenza, National Surveillance of Dally Influenza Outpatients (Daily Case Reporting: DCR), and Mailing-List-Based Influenza Epidemic Database (MLflu). RESULTS: The seasonal influenza epidemic peak for 2003-2004 was observed on January 30, February 1, and February 2 for sentinel surveillance, DCR, and MLflu. Sales peaks of OTC medicines occured twice in 2003-2004 season, once at the end of the year and once on January 27. Peak OTC sales for common cold medication per pharmacy were preceded by 18, 21, and 13 days for sentinel surveillance, DCR, and MLflu. OTC sales successfully explained 74-85% in the variation of influenza incidence which is interpretable as sufficient power of explanation. CONCLUSIONS: OTC sales proved to be a good indicator of real-time surveillance for influenza epidemics. Further analysis on multiyear data is needed to demonstrate the robustness of results. To confirm the advantage in the system of real-time syndromic surveillance, it is also necessary to check explanatory power of OTC sales on the variation of influenza incidence with prospective datasets.

[The impact of changing critical values of the early epidemic detection system for infectious disease surveillance in Japan].

INTRODUCTION: It is important to examine how critical values for initiation/termination affect the trend and frequency of epidemic/pre-epidemic warnings with the early epidemic detection system in Japan. Here we looked at the number of epidemic warning/pre-warning weeks and the influence of changing the criteria values for infectious diseases surveillance. METHODS: An epidemic warning is initiated if the number of cases per week per sentinel medical institution exceeds a critical value. A pre-warning for an epidemic is initiated if cases per week per sentinel medical institution exceed a critical value and there is a non-epidemic warning. To determine effects of the criteria values for epidemics/pre-epidemics for warning onset and termination, we set different values and compared the number of weeks of epidemic warning, the proportion of the total observed weeks. Also, pre-epidemic warning measurements were compared. Data from the infectious diseases surveillance system were analyzed from fiscal years 1999 to 2003. RESULTS: When the critical value for warning onset was lowered, the warning week started sooner and ended later. When the critical value was raised, the opposite occurred: the number of weeks with a warning status decreased. When the critical value was changed within a certain range, the number of weeks with a warning status became 0.5 to 2 times larger than those with the defined value. Similar trends were observed when the pre-warning was examined: the number of warning weeks was 0.4 to 2 times (for influenza and chickenpox) and 0.3 to 3 times (for measles and mumps) larger than those with the defined value. Except for pertussis and rubella, the proportion of warning weeks was approximately 5% for all diseases listed in the early epidemic detection system. In addition, there was no distinct issue with the critical values themselves. CONCLUSION: The present examination of linkage between trends and frequencies of epidemic warnings/ pre-warnings and the critical values in the early epidemic detection system of infectious disease surveillance in Japan confirmed the expected increase with lowering of the threshold. Except for pertussis and rubella, there was no distinct issue with the critical values themselves.

A Practitioner-Driven Research Agenda for Syndromic Surveillance.

Syndromic surveillance has expanded since 2001 in both scope and geographic reach and has benefited from research studies adapted from numerous disciplines. The practice of syndromic surveillance continues to evolve rapidly. The International Society for Disease Surveillance solicited input from its global surveillance network on key research questions, with the goal of improving syndromic surveillance practice. A workgroup of syndromic surveillance subject matter experts was convened from February to June 2016 to review and categorize the proposed topics. The workgroup identified 12 topic areas in 4 syndromic surveillance categories: informatics, analytics, systems research, and communications. This article details the context of each topic and its implications for public health. This research agenda can help catalyze the research that public health practitioners identified as most important.

A multilingual ontology for infectious disease surveillance: rationale, design and challenges.

A lack of surveillance system infrastructure in the Asia-Pacific region is seen as hindering the global control of rapidly spreading infectious diseases such as the recent avian H5N1 epidemic. As part of improving surveillance in the region, the BioCaster project aims to develop a system based on text mining for automatically monitoring Internet news and other online sources in several regional languages. At the heart of the system is an application ontology which serves the dual purpose of enabling advanced searches on the mined facts and of allowing the system to make intelligent inferences for assessing the priority of events. However, it became clear early on in the project that existing classification schemes did not have the necessary language coverage or semantic specificity for our needs. In this article we present an overview of our needs and explore in detail the rationale and methods for developing a new conceptual structure and multilingual terminological resource that focusses on priority pathogens and the diseases they cause. The ontology is made freely available as an online database and downloadable OWL file.

Effect of Meteorological and Geographical Factors on the Epidemics of Hand, Foot, and Mouth Disease in Island-Type Territory, East Asia.

Hand, foot, and mouth disease (HFMD) has threatened East Asia for more than three decades and has become an important public health issue owing to its severe sequelae and mortality among children. The lack of effective treatment and vaccine for HFMD highlights the urgent need for efficiently integrated early warning surveillance systems in the region. In this study, we try to integrate the available surveillance and weather data in East Asia to elucidate possible spatiotemporal correlations and weather conditions among different areas from low to high latitude. The general additive model (GAM) was applied to understand the association between HFMD and latitude, as well as meteorological factors for islands in East Asia, namely, Japan, Taiwan, Hong Kong, and Singapore, from 2012 to 2014. The results revealed that latitude was the most important explanatory factor associated with the timing and amplitude of HFMD epidemics (P < 0.0001). Meteorological factors including higher dew point, lower visibility, and lower wind speed were significantly associated with the rise of epidemics (P < 0.01). In summary, weather conditions and geographic location could play some role in affecting HFMD epidemics. Regional integrated surveillance of HFMD in East Asia is needed for mitigating the disease risk.

Using Social Media for Actionable Disease Surveillance and Outbreak Management: A Systematic Literature Review.

OBJECTIVE: Research studies show that social media may be valuable tools in the disease surveillance toolkit used for improving public health professionals' ability to detect disease outbreaks faster than traditional methods and to enhance outbreak response. A social media work group, consisting of surveillance practitioners, academic researchers, and other subject matter experts convened by the International Society for Disease Surveillance, conducted a systematic primary literature review using the PRISMA framework to identify research, published through February 2013, answering either of the following questions: Can social media be integrated into disease surveillance practice and outbreak management to support and improve public health?Can social media be used to effectively target populations, specifically vulnerable populations, to test an intervention and interact with a community to improve health outcomes?Examples of social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs, and discussion forums. For Question 1, 33 manuscripts were identified, starting in 2009 with topics on Influenza-like Illnesses (n = 15), Infectious Diseases (n = 6), Non-infectious Diseases (n = 4), Medication and Vaccines (n = 3), and Other (n = 5). For Question 2, 32 manuscripts were identified, the first in 2000 with topics on Health Risk Behaviors (n = 10), Infectious Diseases (n = 3), Non-infectious Diseases (n = 9), and Other (n = 10). CONCLUSIONS: The literature on the use of social media to support public health practice has identified many gaps and biases in current knowledge. Despite the potential for success identified in exploratory studies, there are limited studies on interventions and little use of social media in practice. However, information gleaned from the articles demonstrates the effectiveness of social media in supporting and improving public health and in identifying target populations for intervention. A primary recommendation resulting from the review is to identify opportunities that enable public health professionals to integrate social media analytics into disease surveillance and outbreak management practice.

Characteristics of geographical spread and temporal accumulation of the 2009 influenza A (H1N1) epidemic in Japan Based on National Surveillance Data.

This study aimed to describe the geographical spread and temporal accumulation of cases during the 2009 influenza A (H1N1) epidemic in Japan. Using a method adopted by the National Epidemiological Surveillance of Infectious Diseases (NESID) to identify epidemics, we described the frequency and temporal change of the 2009 influenza A (H1N1) epidemic among designated public health center areas in Japan. We calculated the proportion of public health center areas with an epidemic by week from 1999 to 2010. The 2009 influenza A (H1N1) epidemic had several distinguishing features compared with previous seasonal influenza epidemics. For example, the 2009 epidemic started in autumn and peaked at week 49, almost 10 weeks earlier than that of previous seasonal influenza epidemics. Additionally, the 2009 epidemic had the highest total number of public health center areas reporting an epidemic within a season, but only the second highest proportion of areas with an epidemic in the peak week (78.5%). The duration of the epidemic was 17 weeks, which was longer than that of previous epidemics. The present study results shed light on the epidemiology of the 2009 influenza A (H1N1) pandemic and provide useful information to create strategies to prevent future pandemics.

Interfacing a biosurveillance portal and an international network of institutional analysts to detect biological threats.

The Early Alerting and Reporting (EAR) project, launched in 2008, is aimed at improving global early alerting and risk assessment and evaluating the feasibility and opportunity of integrating the analysis of biological, chemical, radionuclear (CBRN), and pandemic influenza threats. At a time when no international collaborations existed in the field of event-based surveillance, EAR's innovative approach involved both epidemic intelligence experts and internet-based biosurveillance system providers in the framework of an international collaboration called the Global Health Security Initiative, which involved the ministries of health of the G7 countries and Mexico, the World Health Organization, and the European Commission. The EAR project pooled data from 7 major internet-based biosurveillance systems onto a common portal that was progressively optimized for biological threat detection under the guidance of epidemic intelligence experts from public health institutions in Canada, the European Centre for Disease Prevention and Control, France, Germany, Italy, Japan, the United Kingdom, and the United States. The group became the first end users of the EAR portal, constituting a network of analysts working with a common standard operating procedure and risk assessment tools on a rotation basis to constantly screen and assess public information on the web for events that could suggest an intentional release of biological agents. Following the first 2-year pilot phase, the EAR project was tested in its capacity to monitor biological threats, proving that its working model was feasible and demonstrating the high commitment of the countries and international institutions involved. During the testing period, analysts using the EAR platform did not miss intentional events of a biological nature and did not issue false alarms. Through the findings of this initial assessment, this article provides insights into how the field of epidemic intelligence can advance through an international network and, more specifically, how it was further developed in the EAR project.

Qualitative analysis of the perception and acceptability of pathogen transport among housewives using focus group interviews.

We conducted focus group interviews to understand how residents of Japan feel about the transport of pathogens. Twelve randomly selected housewives, who had no special knowledge regarding the topic before the interview, expressed their opinions in 2 separate meetings regarding pathogen transport. The results of the interviews were analyzed by the KJ method. The analysis found that although the transport of pathogens is universally recognized to be necessary, there is not clear consensus on the exact methods of transport, the positive and/or negative value of such information, and how clearly and/or uniquely to label containers, packages, compartments, vehicles, and conditions used for such transportation. Further studies to improve the skills of both the providers and receivers of such information (a technique of risk communication) are necessary.

Risk parameters of fulminant acute respiratory distress syndrome and avian influenza (H5N1) infection in Vietnamese children.

A clinical picture of patients with acute respiratory distress syndrome (ARDS) induced by highly pathogenic avian influenza A (H5N1) has been reported. We reviewed 37 sets of clinical data for pediatric patients with ARDS at the National Hospital of Pediatrics (Hanoi, Vietnam); 12 patients with H5N1-positive and 25 with H5N1-negative ARDS were enrolled. The H5N1-negative patients had a clinical picture and mortality rate similar to that for the pediatric ARDS patients. However, the H5N1-positive patients had ARDS with normal ventilation capacity at the time of hospital admission, then rapidly proceeded to severe respiratory failure. The survival probability and days until final outcome in groups of H5N1-positive (n=12) vs. H5N1-negative (n=25) patients were 17% versus 52% and 12.3+/-5.7 days (median, 11 days) versus 21.5+/-13.8 days (median, 22 days), respectively. Our observations clarified the clinical picture of H5N1-induced fulminant ARDS and also confirmed that relatively older age (approximately 6 years of age), high fever at onset, and leukopenia and/or thrombocytopenia at the time of hospital admission are risk parameters for H5N1-induced fulminant ARDS.

Preparedness for the spread of influenza: prohibition of traffic, school closure, and vaccination of children in the commuter towns of Tokyo.

In Greater Tokyo, many people commute by train between the suburbs and downtown Tokyo for 1 to 2 h per day. The spread of influenza in the suburbs of Tokyo should be studied, including the role of commuters and the effect of government policies on the spread of disease. We analyzed the simulated spread of influenza in commuter towns along a suburban railroad, using the individual-based Monte Carlo method, and validated this analysis using surveillance data of the infection in the Tokyo suburbs. This simulation reflects the mechanism of the real spread of influenza in commuter towns. Three measures against the spread of influenza were analyzed: prohibition of traffic, school closure, and vaccination of school children. Prohibition of traffic was not effective after the introduction of influenza into the commuter towns, but, if implemented early, it was somewhat effective in delaying the epidemic. School closure delayed the epidemic and reduced the peak of the disease, but it was not as effective in decreasing the number of infected people. Vaccination of school children decreased the numbers not only of infected children but also of infected adults in the regional communities.

Epidemics of influenza and pediatric diseases observed in infectious disease surveillance in Japan, 1999-2005.

BACKGROUND: A method for determining epidemics in small areas from the sentinel surveillance data has been proposed and applied in the National Epidemiological Surveillance of Infectious Diseases (NESID) in Japan. We observed epidemics of influenza and 11 pediatric diseases by the method in the NESID in Japan during 1999-2005. METHODS: We assumed that an epidemic in a public health center area began in a week when the number of cases reported to the NESID per sentinel clinic and hospital in the area in the week exceeded a given value, and that the epidemic ended when the number was lower than another given value. The proportion of public health center areas with epidemics (epidemic area proportion) by week in fiscal 1999-2005 was calculated. Total public health center area-weeks observed were about 30,000 each year. RESULTS: The mean epidemic area proportion in the 7 years was 6.0% for influenza and 0.2-7.4% for pediatric diseases. The proportion increased in pharyngoconjunctival fever and group A streptococcal pharyngitis, decreased in measles and was less than 1.0% in pertussis and rubella. In influenza, the height of the peak in the weekly epidemic area proportion varied between 6 and 90% in the 7 years and the week of the peak varied widely. In some pediatric diseases, the height of the peak varied, while the week of the peak was relatively constant. CONCLUSION: The frequency and temporal change were described in the epidemics of influenza and pediatric diseases in public health center areas from the NESID data in Japan, 1999-2005.