Bioterrorism is a public health threat that is designed to cause panic in the community through the intentional dispersal of a pathogenic virus, microbe, or toxin. Biological attacks, both worldwide and in Japan, have been attempted multiple times over the past century.Reference Christopher, Cieslak and Pavlin 1 In Japan, counterterrorism measures have been developed, largely as the result of a series of national and international events.Reference Sugishima 2 International security concerns, including the experimental launching of ballistic missiles by North Korea in 1998, the tragic September 11 terrorist attacks, and subsequent anthrax exposures in 2001 in the United States have all impacted Japanese policy. In Japan, the chemical and biological attacks conducted by the Aum Shinrikyo religious cult group in 1992 further highlighted the need for preparedness measures. Shoko Asahara (head of Aum Shinrikyo during the Tokyo subway gas attack) and his followers have also visited Zaire to obtain samples of the Ebola virus for the development of biological agents.Reference Broad 3
Unfortunately, bioterrorism remains a concern, given that the development of biological agents was sponsored at a national level (eg, the former Soviet Union) and this technology is readily obtainable. Current biological weapons possess pandemic potential given the population density of urban areas, rapid inter-region transportation, and the enclosed environments of modern buildings. Smallpox is well known as an acute and highly contagious disease that is typically spread by direct and face-to-face contact and that has devastated populations throughout history. The fatality rate is estimated at up to 30%, and a rapid airborne outbreak facilitated by air circulation systems has been observed in the past.Reference Wehrle, Posch and Richter 4 In 1980, the World Health Organization (WHO) declared that “there is no evidence that smallpox will return as an endemic disease.” 5 As routine vaccinations have been terminated, immunity has decreased over time in the older vaccinated populations, and the younger unvaccinated population is left completely unprotected.
In response to these vulnerabilities, smallpox is now considered a significant bioterrorism threat, and health authorities are forced to strengthen their ability to sustainably manage the potential public health emergency.Reference Henderson and Arita 6 The purpose of this article was to introduce current activities that have been developed to identify and suppress potential contagious bioterrorism threats in Japan. As well, the contribution of public health preparedness to domestic and international health security is discussed.
Narratives
The Impact of “Dark Winter” and the Establishment of a Domestic Framework for Managing Bioterrorism
In June 2001, a simulation exercise entitled “Dark Winter” was carried out in the United States to allow senior policy makers to develop a response to a hypothetical biological attack. Dark Winter simulated the deliberate introduction of smallpox in several states during the winter of 2002, with 300,000 individuals becoming infected within 3 weeks of initial exposure. Owing to low supplies of the smallpox vaccine, Dark Winter estimated that over 3,000,000 individuals would eventually become infected. These results revealed that the general population’s lack of immunity would render it highly susceptible to smallpox infection, as more than 30 years had passed since vaccination was discontinued. Therefore, a local biological attack with a contagious pathogen could rapidly become a national or international crisis and could cripple the target country.Reference O’Toole, Mair and Inglesby 7 After Dark Winter, researchers analyzed outbreak patterns for populations with or without immunity.Reference Zenihana and Ishikawa 8 These estimations form the basic reference for a possible smallpox pandemic and are useful for calculating the number of vaccinations needed. The results of Dark Winter have had important policy implications, with additional studies regarding pandemic simulation using the basic model described in this exercise.
After the September 11 attacks, the Chemical, Biological, Radiological and Nuclear (CBRN) countermeasure model was established to create a multidisciplinary and cross-sectional platform for collaboration between various authorities to ensure a standardized national response system for all threats. In this system, local government is largely responsible for management at the site of the incident in collaboration with police, fire, and other emergency services. Various tabletop exercises have been performed regarding pandemic simulations, and health care workers of the local health office, quarantine station, and community hospital are regarded as first responders. These individuals are the first to contact infected patients, and their protection (including vaccination) must be considered a first priority.
Japanese national research has also supported the development of a pandemic simulation model to estimate the impact of biological attacks. The Japanese government, in particular the Ministry of Health, Labour, and Welfare, is largely responsible for medical activities in cases of public health emergency and coordinates with other security authorities to manage outbreaks. If a major national incident were to occur, accurate intelligence might not be readily available, highlighting the importance of health authorities, law enforcement, and other agencies sharing the information. Planning at the individual, family, community, and national levels is critical to creating the relationships necessary for an effective response.
Regulations for Control of Infectious Diseases and Biological Incidents
The frequent occurrence of emerging avian influenza in Southeast Asia has been critical in drawing attention to the need for countermeasures for infectious disease in Japan. In response, the Japanese government promulgated the Infectious Diseases Control Law to create a comprehensive management system for such highly contagious pathogens. The objective of this law is to reduce the possibility of a pathogen’s accidental or intentional release by improving surveillance, laboratory safety, pathogen collection, and sample transportation. Government officials are legally entitled to enter all relevant facilities to investigate the proper storage of pathogens. In addition, this law requires local governments to implement 4 unique measures: enforcement of an active epidemiological survey, preparation of an action plan in case of a serious infectious disease outbreak, education of government officials and health care workers regarding biological weapons, and designation of a hospital as a fixed observation point during outbreaks.Reference Okabe 9 The spread of emerging infection, transmitted by multiple travelers, resulted in the introduction of a rigorous quarantine and isolation system.
National Institutes Play a Central Role in Infectious Disease Control
The Japanese biodefense program has largely been driven by contributions from several national institutes. The National Institute of Infectious Diseases (NIID) has played an important role as a central institute in Japan. Major functions of the NIID are basic research, reference services, surveillance programs, sample collection, data analysis, distribution of information, quality control for vaccines, and international collaboration. The NIID has also organized the Infectious Diseases Surveillance Center (IDSC), which plays a central role in Japan’s surveillance system. Serving as a member of the WHO, the NIID has made efforts to enhance international partnerships, agreeing to a global memorandum to promote research collaboration, human resource development, and sharing of information.
Under the Infectious Diseases Control Law, the NIID conducts routine surveillance of infectious diseases. The 2008 Japanese G8 summit provided an opportunity to upgrade Japan’s biodefense surveillance system. During this event, the IDSC conducted syndrome surveillance monitoring by using drug marketing data. Although there was no notable outbreak during the event, the importance of an automated surveillance system was realized as a result of this event.Reference Ohkusa, Yamaguchi and Sugihara 10
On the other hand, the National Institute of Public Health (NIPH) conducts research, human resource development, and public health initiatives in Japan. The NIPH has made important contributions to the prevention of incidents affecting public health, including pandemic disease. The NIPH holds a training program called the “Health Crisis Management Course,” which educates community health care workers in the acquisition of public health information. Workers can upload current data by using a system entitled the “Health Crisis Management Library System (H-CRISIS),” which allows local public health authorities to promptly gather and evaluate information regarding health risks.Reference Tanihata, Okumura and Mizushima 11 Human resources are critical to adequate pandemic control, and both the NIID and the NIPH are key organizations with the capacity to improve public health emergency management skills.
Development of Safer Vaccines and Vaccination Policies
During the WHO smallpox eradication campaign, Japanese scientists developed a highly attenuated, third-generation vaccine called LC16m8. The new vaccine was derived from the Lister strain commonly used in the WHO program and was selected for temperature sensitivity and pock size through plaque cloning and cell culture of rabbit kidney cells. Clinical trials in the 1970s, which enrolled approximately 100,000 infants, revealed that the induced immunity level was similar to that of the Lister strain without any of the serious adverse events.Reference Hashizume 12 LC16m8 is known to induce fewer neurotoxicity and dermal reactions, because it lacks the B5R gene that encodes the envelope protein. Although LC16m8 has never been used to prevent smallpox in the field, an animal model of Orthopoxvirus infection showed adequate immunogenic reaction to LC16m8 as well as a full protective effect.Reference Hashizume 12 A recent study by Japan Self-Defense Forces (JSDF) personnel found immunogenicity in vaccine-naïve adults as well as an excellent booster effect in previously vaccinated individuals (no serious adverse events were observed).Reference Saijo, Ami and Suzaki 13 These findings indicate that LC16m8 is a good candidate for national use, given its high safety and immunogenicity. Although vaccination is the only effective tool for controlling smallpox, the global eradication program has made it possible to discontinue routine global vaccination. In the past, smallpox was targeted to military personnel, although there has been a recent shift to potentially targeting civilians, which would result in enormous individual, social, and economic harm. Concerning emergency preparedness, the potentially susceptible population must be estimated, and a national vaccination policy developed. In Japan, the current supply of smallpox vaccine is exclusively LC16m8. Although it has never been tested in the field, and further investigation into its use in immunocompromised or atopic cases is important, LC16m8 is a suitable candidate for a national stockpile.
Initiation of Military Response to a Biological Attack
In the event of CBRN weapons that do not correspond to an armed attack, but against which the general police force alone cannot maintain public security, the JSDF will assist in the response. The JSDF will coordinate with public security personnel to suppress a biological attack and assist victims in cooperation with related agencies. In preparation, the JSDF has improved their capability for responding to a CBRN attack by forming the Central CBRN Weapon Defense Unit under the Central Readiness Force and ensuring that each division has a counter-CBRN unit. Upgrades to specialized CBRN equipment are ongoing, including armored reconnaissance vehicles, field detection devices, decontamination vehicles, personal protective gear, portable automatic biological sensors, and new decontamination kits. In addition, the JSDF has designated personnel to take immediate action in CBRN events, which will facilitate a response in approximately 1 hour. The JSDF has also engaged in efforts to establish and improve partnerships with relevant external institutions, including local authorities and police and fire departments. These efforts include launching the first-ever joint training exercise for civil protection in preparation for possible terrorism.
Discussion
Extensive efforts have been made to ensure that national and international relationships are available to support the response system if the emergency requirements exceed normal medical resources. In this section, we examine integration of expertise and the provision of a sustainable response in the case of a smallpox pandemic.
Strengthening Public Health Capacity Against Bioterrorism
One specialist stated the opinion that although the risk of a large-scale biological incident is not high, unless the international community takes decisive action, there is still a concern that biological attacks could be used by terrorist groups.Reference Saito, Fujii and Kanatani 14 In such a case, first responders would include rescue workers, security personnel, health care providers, and clinicians, all working together to contain the public health emergency. Therefore, every responder is expected to play a pivotal role and can prepare by fostering strong and responsible partnerships. To this end, each responder must understand how to organize and utilize all available resources in order to support optimal outcomes.
During the initial phase, the most important consideration is establishing an effective command structure. The Incident Command System (ICS) provides a relevant command structure that can produce solutions in the face of difficult situations. The ability of the ICS to integrate multiple local and national organizations into a coordinated response makes it particularly suitable for use during biological attacks.Reference Graham and Talent 15 To strengthen Japan’s surge capacity against a biological attack, the ICS plays an important role in the current incident response training. To manage the large number of patients, most key hospitals employ medical staff who have been trained in implementing the ICS during emergencies to efficiently manage resources and personnel.
Promoting Cooperation With International Society
Although emerging infectious diseases may be of great concern to national security, they may also directly affect human health throughout the world. The Global Health Security Initiative (GHSI) is an international partnership intended to strengthen global responses to CBRN threats and pandemic diseases. This partnership was launched in 2001 by ministers of health from Canada, the European Union, France, Germany, Italy, Japan, Mexico, the United Kingdom, and the United States (the WHO serves as an expert advisor). The GHSI was envisaged as an informal group to allow like-minded countries to address health issues of the day, including global health security. According to the recent ministerial meeting in 2013 in Italy, the GHSI has recognized the significance of shared medical information in facilitating public health preparedness for pandemic events.Reference Burkle, Hsu and Loehr 16 Lessons learned from past outbreaks (eg, avian flu, SARS) indicate that a global network that shares laboratory, sample, and patient information is essential to expediting research and epidemiological surveillance. Japan, as a member of the international community, has recognized the need to take action to meet the health and security needs of the global population.
The new International Health Regulations (IHR) adopted at the WHO assembly of 2005 address an international concern that national borders cannot prevent the spread of infectious diseases, especially those that are airborne. The IHR improves global surveillance, alerts, and response, and all countries, especially industrialized countries, are required to strengthen their existing public health capacity and to contribute to international collaboration. 17 Preventing pandemics requires early detection and containment of any suspicious outbreak, and the international surveillance laid out in the IHR depends upon flexible public health systems and multilateral cooperation.
Conclusion
Although bioterrorism may seem like a distant threat, it is important to note that biological agents have been used throughout history and effective responses should be prepared. Many hospitals must improve their response plan through annual training exercises with local health officials, which will further strengthen the national capability to respond appropriately to a biological attack. The most effective response to biological attacks requires close coordination between clinical facilities and public health agencies. Medical and emergency professionals should become familiar with relevant biological agents, which will allow them to manage pandemic situations. Through these steps, individuals contribute to both domestic and international health security.
Acknowledgments
This study was supported by research funding from the Japan Ministry of Health, Labour, and Welfare in fiscal year 2013.
