Tamie Sugawara

Real-time prescription surveillance and its application to monitoring seasonal influenza activity in Japan

Background Real-time surveillance is fundamental for effective control of disease outbreaks, but the official sentinel surveillance in Japan collects information related to disease activity only weekly and updates it with a 1-week time lag. Objective To report on a prescription surveillance system using electronic records related to prescription drugs that was started in 2008 in Japan, and to evaluate the surveillance system for monitoring influenza activity during the 2009–2010 and 2010–2011 influenza seasons. Methods We developed an automatic surveillance system using electronic records of prescription drug purchases collected from 5275 pharmacies through the application service provider’s medical claims service. We then applied the system to monitoring influenza activity during the 2009–2010 and 2010–2011 influenza seasons. The surveillance system collected information related to drugs and patients directly and automatically from the electronic prescription record system, and estimated the number of influenza cases based on the number of prescriptions of anti-influenza virus medication. Then it shared the information related to influenza activity through the Internet with the public on a daily basis. Results During the 2009–2010 influenza season, the number of influenza patients estimated by the prescription surveillance system between the 28th week of 2009 and the 12th week of 2010 was 9,234,289. In the 2010–2011 influenza season, the number of influenza patients between the 36th week of 2010 and the 12th week of 2011 was 7,153,437. The estimated number of influenza cases was highly correlated with that predicted by the official sentinel surveillance (r = .992, P < .001 for 2009–2010; r = .972, P < .001 for 2010–2011), indicating that the prescription surveillance system produced a good approximation of activity patterns. Conclusions Our prescription surveillance system presents great potential for monitoring influenza activity and for providing early detection of infectious disease outbreaks.

Social contacts, vaccination decisions and influenza in Japan

Background Contact patterns and vaccination decisions are fundamental to transmission dynamics of infectious diseases. We report on age-specific contact patterns in Japan and their effect on influenza vaccination behaviour. Methods Japanese adults (N=3146) were surveyed in Spring 2011 to assess the number of their social contacts within a 24 h period, defined as face-to-face conversations within 2 m, and gain insight into their influenza-related behaviour. We analysed the duration and location of contacts according to age. Additionally, we analysed the probability of vaccination and influenza infection in relation to the number of contacts controlling for individuals characteristics. Results The mean and median reported numbers of daily contacts were 15.3 and 12.0, respectively. School-aged children and young adults reported the greatest number of daily contacts, and individuals had the most contacts with those in the same age group. The age-specific contact patterns were different between men and women, and differed between weekdays and weekends. Children had fewer contacts between the same age groups during weekends than during weekdays, due to reduced contacts at school. The probability of vaccination increased with the number of contacts, controlling for age and household size. Influenza infection among unvaccinated individuals was higher than for those vaccinated, and increased with the number of contacts. Conclusions Contact patterns in Japan are age and gender specific. These contact patterns, as well as their interplay with vaccination decisions and infection risks, can help inform the parameterisation of mathematical models of disease transmission and the design of public health policies, to control disease transmission.

Real-time estimation and prediction for pandemic A/H1N1(2009) in Japan

The Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Japan, has developed a fully automatic system for daily reporting of ILI (influenza-like illness) patients prescribed Oseltamivir and Zanamivir. The system collected data on the number of prescriptions from approximately 3350 pharmacies, which account for almost 7% of all pharmacies in Japan, and published the number online on a daily basis, except for Sundays. On the basis of these data, we further estimated Rv and predicted its course every Monday using a very simple SIR model with data from previous studies. This paper summarizes our real-time estimation and prediction of ILI patients in the 2009 influenza A/H1N1 pandemic. The estimate on November 29 resulted in an Rv of 1.72 (95%CI [1.69, 1.75]). The model predicted that the peak of the epidemic would be reached on December 23 2009 [December 14, 2009, January 2, 2010] with an estimated number of ILI patients of 227,000 [193,000, 262,000]. The cumulative number of ILI patients over the period would be as high as 17.8% [16.6, 19.0%] of the total population of Japan. This information was circulated weekly among central and local government officers in charge of pandemic control to provide updates on the pandemic situation and to aid their decision-making on control strategies. In conclusion, for the first time in the world, we successfully demonstrated real-time estimation and prediction for the entire course of a pandemic, and which could be used routinely for planning counter-measures.

Evaluation of estimated number of influenza patients from national sentinel surveillance using the national database of electronic medical claims.

Officially, the national official sentinel surveillance of infectious diseases (NOSSID) has been used to estimate the number of influenza patients nationwide; NOSSID is based on the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (the Infectious Diseases Control Law). Prescription Surveillance (PS) has also provided a numerical estimate of influenza patients. This study compared these 2 estimations using NOSSID and PS with the numbers of influenza patients from all electronic medical claims (NDBEMC), which had the nearly-comprehensive data from surveys. Results showed that the estimate from NOSSID was about twice the estimate from the NDBEMC. However, the estimated number from the PS was almost equivalent to that from the NDBEMC. The estimated number of patients from NOSSID might not be precise, but NOSSID itself may be useful to monitor influenza trends.

Abnormal behavior during influenza in Japan during the last seven seasons: 2006–2007 to 2012–2013

A few mortalities and cases of severe abnormal behavior have been reported after oseltamivir administration for influenza, thus increasing medical and public concerns regarding the drugs safety. We investigated the association between oseltamivir and abnormal behavior for seven years. All outpatient clinics and hospitals all over the country were requested to report severe abnormal behavior that could have resulted in a fatality if nobody intervened, such as abrupt running outside the home or intention of jumping off a building. The survey was performed prospectively between the 2007-2008 and 2012-2013 seasons, and retrospectively for the 2006-2007 season. As the result of the investigation, eight-hundred fifty-eight cases were reported and among of them 95.7% were positive by the influenza rapid diagnosis test. The epidemic curve of severe abnormal behavior showed a pattern similar to influenza-like illness. The same pattern was observed regardless of age group, gender, or timing of the incidents after waking. Consequently, specific association between the types of medications used or the types of antiviral and abnormal behavior was not observed clearly. The reported abnormal behaviors include fatal cases that would have died if nobody had stopped. This suggested that patients with influenza should be observed with caution for possible abnormal behavior whether taking oseltamivir or other neuraminidase inhibitor anti-influenza drugs.

Ongoing increase in measles cases following importations, Japan, March 2014: times of challenge and opportunity.

WPSAR Vol 5, No 2, 2014 | doi: 10.5365/wpsar.2014.5.2.001 www.wpro.who.int/wpsar 1 a Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan. b Department of Virology 3, National Institute of Infectious Diseases, Tokyo, Japan. Submitted: 1 April 2014; Published: 16 May 2014 doi: 10.5365/wpsar.2014.5.2.001 Ongoing increase in measles cases following importations, Japan, March 2014: times of challenge and opportunity

Life-Threatening Abnormal Behavior Incidence in 10-19 Year Old Patients Administered Neuraminidase Inhibitors.

Much discussion has surrounded the association between the administration of neuraminidase inhibitors (NI) and severe abnormal behaviors, including sudden running away and jumping from a high place, which can be life-threatening if no one intervenes. Using data on the number of abnormal behaviors and patients who had been prescribed NI in Japan, we calculated the incidence rate of severe abnormal behaviors among influenza patients who had been prescribed NI. Then, we evaluated the relative risk between the four types of NI on severe abnormal behavior. We found no significant difference in the incidence rates of abnormal behavior by the type of NI. Results implicate that the current policy of package inserts, which warn physicians that patients who were administered ANY type of NI might exhibit abnormal behavior, seems to be appropriate.

Prescription surveillance and polymerase chain reaction testing to identify pathogens during outbreaks of infection.

Syndromic surveillance, including prescription surveillance, offers a rapid method for the early detection of agents of bioterrorism and emerging infectious diseases. However, it has the disadvantage of not considering definitive diagnoses. Here, we attempted to definitively diagnose pathogens using polymerase chain reaction (PCR) immediately after the prescription surveillance system detected an outbreak. Specimens were collected from 50 patients with respiratory infections. PCR was used to identify the pathogens, which included 14 types of common respiratory viruses and Mycoplasma pneumoniae. Infectious agents including M. pneumoniae, respiratory syncytial virus (RSV), rhinovirus, enterovirus, and parainfluenza virus were detected in 54% of patients. For the rapid RSV diagnosis kit, sensitivity was 80% and specificity was 85%. For the rapid adenovirus diagnosis kit, no positive results were obtained; therefore, sensitivity could not be calculated and specificity was 100%. Many patients were found to be treated for upper respiratory tract infections without the diagnosis of a specific pathogen. In Japan, an outbreak of M. pneumoniae infection began in 2011, and our results suggested that this outbreak may have included false-positive cases. By combining syndromic surveillance and PCR, we were able to rapidly and accurately identify causative pathogens during a recent respiratory infection outbreak.

Enhanced Surveillance for the Sports Festival in Tokyo 2013: Preparation for the Tokyo 2020 Olympic and Paralympic Games

Enhanced surveillance was conducted during the Sports Festival in Tokyo 2013 (September 28-October 14, 2013) for early detection of outbreaks of infectious diseases and other health emergencies. Through this enhanced surveillance, 15 cases were found that required additional gathering of information outside the routine process of creating/evaluating the Daily Report. However, none of these was assessed as critical. Through the enhanced surveillance, we structured a framework that allows for earlier response when detecting aberrations. It includes the role of the Tokyo Metropolitan Government in communications and contacts with relevant parties such as public health centers, as well as in monitoring of surveillance data. However, some issues need to be further considered toward the Tokyo 2020 Olympic and Paralympic Games, such as establishing the criteria for additional response steps, increasing the number of participating bodies in syndromic surveillance, and strengthening of cooperation with related departments, including those for crisis management assuming potential biological/chemical terrorism.

Short-term Prediction of the Incidence of Congenital Rubella Syndrome.

Objectives In Japan, a rubella outbreak occurred from early 2012 to late 2013, primarily among adult males aged 20–49 years. We conducted this study to predict the number of congenital rubella syndrome (CRS) cases in Japan in 2014. Methods The probability of CRS when a pregnant woman is infected with rubella depends on the gestational age of the fetus. The cumulative number of CRS cases was predicted by a formula based on the parameters from two studies conducted in the U.K. and the U.S., the reported cases of rubella among women 15–49 years of age, and the reports of CRS from 2011 to week 2 of 2014. Findings While the predicted number of cases of CRS based on parameters from the U.K. study demonstrated a biphasic curve, with a low peak around week 12 and a high peak around week 50 of 2013, the predicted number of CRS cases based on the U.S. study demonstrated a single peak around week 50 of 2013. The ex post evaluation indicated that the cumulative number of CRS cases in 2014 would be 19.1–29.3. Interpretation Our prediction of the number of CRS cases may be useful for the enhanced detection of this often under-reported syndrome.