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One of the most important types of terrorism is bioterrorism which involves deliberate and illegal use of biological agents, poisonous substances or chemical agents causing mortality and illness in humans, animals and plants. The purpose of such materials is to cause great damage while using a small amount [1-3]. The most important and the most dangerous bioterrorism factors are Anthrax (Bacillus anthracis), Smallpox (variola major) and Viral hemorrhagic fevers(including Filoviruses (Ebola).The most appropriate classification for bioterrorism agents belongs to CDC (Centers for Disease Control and Prevention), which classifies the factors into three categories based on their risk level [4-8]. Potential bioterrorism has some features and factors making it a major threat to national security. That is why terrorists tend to use it more than other weapons of mass destruction. In comparison to nuclear weapons, biological agents have no destructive effects [9]. The bioterrorism agents are more powerful, simpler to provide, less costly, less sophisticated but more lethal. There is also a diversity of agents for the dissemination of biological substances [10-13]. Bioterrorism weapons are not comparable in terms of diversity and scope of action with other weapons [14]. Concerns related to the spread of a disease caused by bioterrorism in society are much more further than the explosion caused by other war weapons [3,13]. On the other hand, the specific characteristics of biological materials and the development of genetic changes in biological warfare agents, together with other factors, have made it more difficult to identify and recognize these factors, and to treat the diseases caused by them [14-18]. Bioterrorism is a real and significant threat of the 21stcentury [19,20]. Which overshadows stability, national security, economic development, and the development process of countries. This kind of terrorism, more than before, has been considered as a remerging and asymmetric health problem, and is now considered an emergency state of national security for many countries. The solution to this problem is to provide a Bioterrorism Information System [21-24]. Hence a large budget has been allocated to research and development of Bioterrorism Information Systems by different countries [6,12,25]. The effectiveness of the Bioterrorism Information System is based on collection and accurate statistical analysis of data about bioterrorism attacks. The basis of this system is information obtained from patients or suspected cases [6,26,27] that are effective in identifying early bioterrorism attacks. This system helps to identify bioterrorism outbreaks using signs, symptom, laboratory findings and other non-clinical information from various sources before confirming final diagnosis. It is also designed to monitor bioterrorism events and to reduce mortality as well as illness. On the other hand, this system is possible to improve the method of response and communication to obtain the clinical details of diseases caused by bioterrorism, what is more, it leads to preservation and promotion of national security [28-34]. The findings of various studies have shown that Bioterrorism Information System can pursue numerous therapeutic, epidemiological, secure and healthy goals with indicators such as high sensitivity and specificity, timeliness and flexibility. These objectives include: Facilitating the accurate and rapid recognition of bioterrorism-related diseases, improving the speed of analysis and data transmission, providing detailed information for evaluating bioterrorism attacks, assisting in determining exposure sites through GIS (Geographic Information Systems), facilitating the integration of bioterrorism information through the country, helping to accomplish effective services, such as the process of vaccination and antibiotic therapy, helping to treat early-onset illnesses leading to death quickly, evaluating the success in the inhibition of disease along with reducing its burden in the area, intercepting the chain or the transmission of secondary diseases, providing historical data to be used as a base for statistical comparisons and long-term monitoring of health [32,33,35]. The effects of Bioterrorism Information System depend on its features. Therefore, the purpose of this study is to survey the features of Bioterrorism Information System.

To conduct this review study, the keywords Sentinel Surveillance, Disease Outbreaks, Bioterrorism, Information systems and Biosurveillance were firstly obtained in 150 articles from databases like Science Direct, Pro Quest, Pub Med, Sid, Springer, Google scholar and Web of Science in the period from 1980 to 2017. After reviewing the titles and abstracts of these articles, 40 were excluded due to nonalignment with the objectives of the study but110 met the requirement of the study. Having analyzed the quality of the articles, the authors identified and used 79 studies as the main ones, based on the contents of the articles and their sources.

Bioterrorism Information System has been widely developed in different countries under different titles for the early detection and rapid control of epidemics as well as their evaluation. One of the features of this system is timely response and reaction. This means that bioterrorism attacks are reported before clinically recognizing the cluster of diseases [36,37]. Bioterrorism Information System with numerous features in the field of data collection and processing, and information distribution, as well as legal and security requirements can reduce epidemiological effects, rate of disease transmission and burden of disease in the community. Finally, more appropriate healthy response and, as a result, an increase in national security are the outcomes of implementation such system [38-40]. Hughes announced that a bioterrorism information system has a real-time surveillance capability and is capable of rapidly exchanging information at the national and regional level, which will help to strengthen the health and security system [32]. In this regard, the Statistics Committee in Defense and National Security (DNS) emphasized the importance of the existence of Bioterrorism Information System because of its secure communication network and power of statistical analysis of incidents [6]. Research results have shown that Bioterrorism Information System, using powerful tools and technologies, new statistical and mathematical models, using GIS, rapid and effective transmission of information to responsible authorities, can help to respond the bioterrorism events [7,13]. Considering the importance of Bioterrorism Information System and its ability for real-time bioterrorism outbreak detection, its development has been prioritized by different countries. For this reason, from 2001 to 2014, there has been an increase in funding for creation and development of such system in security and health organizations of the United States, the United Kingdom and Australia [41-46]. Centers for Disease Control and Prevention (CDC) in America uses various information systems such as Biosurveillance, BioSense, B-SAFER, Biodefend, RSVP and BioStorm to detect and manage bioterrorism events [6,39,47-50]. It should be noted that relying on ontology and problem-solving methods are important features of BioStorm which is also a knowledge-based system [3,50-52]. Equipping the Bioterrorism Information System with advanced detectors based on genome and PCR technologies will increase its validity and sensitivity. Also, the strengths of the Biowatch system include increasing the speed and accuracy of detecting bioterrorism events, and its equipping with robust and highly sensitive detectors [3]. Each of the features of the information system has specific capability. For example, in the data collection phase, FACTS¹ technology (a data integrator system) reduces data redundancy and increases accuracy, completeness and timeliness [46]. The use of diverse data sources increases the power of Bioterrorism Information System in detecting attacks [53]. Also, the results of studies have shown that, in order to increase the accuracy, various systems of bioterrorism surveillance use different data sources [54]. These sources of data are one of the requirements to assess the timely detection of bioterrorism events [55]. Biosurveillance, BioSense, B-SAFER, Biodefend, RSVP in the United States, and Syndromic Surveillance System in England are well known to use the accurate and diverse data sources including Non-clinical data sources such as OTC (Over-The-Counter medicines), school and workplace absenteeism data [37,47-50,54,55]. In Japan and Scotland, the features of the Bioterrorism Information System are based on the clinical and non-clinical data, and also on populationbased behavior. The first category includes data such as data based on emergency departments, the cause of death, information from general physicians (GPs), poison centers, and laboratories. In the second part are there information such as: evaluating the searched words from the internet, nurse hotline, social media surveys, school and workplace absenteeism, and OTC data [40,56]. Another important feature of the Bioterrorism Information System is its syndromic Surveillance. The emphasis of this type of surveillance is on the symptom illness. This system compared with traditional disease surveillance that is based on the final diagnosis, requires less time to detect the outbreak of bioterrorism. This feature has been introduced as a real-time detection [40,57]. BioPortal has the attribute of using the reliable and strong prospective and retrospective statistical methodsm [50,58] in the United States. ESSENCE is well known for its robust processing feature using spatial and temporal detection methods and the use of a combination of military and civilian information [50,59,60]. In America, BioSense uses the statistical method of SPC² and an exact analysis to detect bioterrorism attacks [54,55]. EpiSPIRE, RODS, and LEADERS in the United States [48-50,57,61,62] and ISS³ in China work based on a precise and accurate display and dissemination methods such as Dashboards and GIS [63]. NBSSDP⁴ and LEADERS⁵ in the US have security requirements [31,49,50,64]. Korea’s Bioterrorism Information System has an automatic and timely statistical analysis system, produces reports, and creates an automatic notification system to inform specialists .Its other feature is its reliance on emergency department data [65]. Other notable features of the Bioterrorism Information System are that this system has met the validated legal requirements and has the international telecommunication network via connecting to the security centers and following the guidelines developed by these organizations. This feature is in IDSP⁶ system in India [7] and RODS in the United States as a factor in expediting outbreak detection [48,50,57,62].

In general, the characteristics of the Bioterrorism Information System (Table 1) can be divided into five general categories according to the methodological steps and main functions of the system [28,57,63,66].

Table 1: Remarkable and significant characteristics of well-known Bioterrorism Information Systems in World related to real-time detection of bioterrorism outbreaks.

Features of the Bioterrorism Information System in the data collection phase

The integration of diverse data obtained from various data sources [33,35,54] Examples include the use of clinical and non-clinical data, such as school absenteeism data [29] and OTC [50].

The Acquisition of essential data in real time using accurate and timely collection methods [66] such as the use of biological detectors, accurate and sensitive biosensors, and data integrator technology [67,68].

Use of Data verification in order to reduce data redundancy, increase the accuracy, completeness and timeliness of data using the advanced technology such as FACTS⁷ [46].

The Acquisition and collection of data from security agencies related to bioterrorism events.

Features of Bioterrorism Information system in the processing phase

The features of classification, organization, analysis and detection of bioterrorism attack are found in this group.

Using coding systems and vocabulary standards [50,69-71].

Using a robust and timely processing system [50,59,66] especially using the prospective and retrospective statistical methods that are valid and flexible to modify sensitivity and specificity thresholds based on time and place [31,50,53,58,64].

Automatic statistical analysis system [65].

Knowledge-based, ontology-based and using the problem-solving methods [50-52].

This feature is relevant to reporting and disseminating information.

Relying on a timely distribution and display method for reporting [63] such as real-time reporting based on the EARS method (Early Aberration Reporting System) [50,53].

Creating an automatic message sending system to inform specialists [65].

The use of information dissemination technology based on time and place such as the use of GIS, dashboards as well as accurate and rapid alert systems [50-52] to increase efficiency for data dissemination. An example for this feature is “use of dashboards in BioWatch” [72].

Using the network to facilitate sharing of data, such as the use of crisis information sharing platform technology (CRISP), Public Health Information Network (PHIN), and National Food Safety Laboratory System (NFSLS) [3,46,63].

Using the alert system for bioterrorism events such as National Bioterrorism Security Advisory System from severe threat (red) to low threat (green) [30].

Features of Bioterrorism Information System related to security requirements

It includes secure and valid coding, acquisition, collection, transmission, storage and delivery of information, with emphasis on maintaining the main attributes of data security such as integrity, availability, and confidentiality [71,73].

Security management and policy making for the Bioterrorism Information System, including risk management [identifying and prioritizing the existing security threats to the Bioterrorism Information System] and security policy management (determining the sanction policy for non-compliance requirements and determining how the information system is accessed by authorized members).

Software system security, with an emphasis on maintaining the basic concepts of security, including integrity, availability, and confidentiality [71,73].

Security in human resources domain [skills, training and experience] such as informing users about the legal consequences of disclosure.

Security in hardware and equipment domain, such as damage assessment (regular scanning of network systems and its infrastructure), ensuring the continuous update of equipment and the existence of instructions to ensure the physical safety of equipment [50,57,59,66].

Security in the collection, processing, storage, transmission and dissemination of information through the use of encryption methods in the data collection phase [60]. Also, compliance with security standards for transmission messages and information in the Bioterrorism Information System [50,57], use of secure communication networks such as Epi-X (CDC’s Epidemic Information Exchange (Epi-X)and BIOTOX and compliance with applicable security laws such as HIPAA and also the use of security technologies like SSL⁸ [40,57,74-77].

Features of Bioterrorism Information System related to legal requirements

Following general standards such as ASTM, HL7, ISO [49,78,79]

Following specific standards of Bioterrorism Information System, such as the PAHPA⁹ [22] and UN Security Council Resolution 1540, and compliance with security requirements and connection to security centers such as the FBI (Federal Bureau of Investigation) [48,50,57,62].

Each Bioterrorism Information System has specific features. But in some of these systems, a feature has been introduced as a significant feature in bioterrorism outbreaks detection.

In general, Bioterrorism Information System in the world is presented in two simple and complex models. The fundamental difference between these two models is related to the time when bioterrorism attacks are identified, so that more sophisticated and more complex systems are more successful and effective in detecting early outbreak. The use of advanced technology varies according to the financial and scientific progress capacity in countries. Its history dates back to September 11, 2001, simultaneously with the release of envelopes containing anthrax spores. Considering the17-year history of the system and advanced technology in the United States, it has increased its capabilities and facilities.

The features of this system that have led to the prominence of this system include:

- Being equipped with detectors and biosensors as data sources

- The use of advanced technologies such as FACTS to integrate data

- Being connected and to security centers and using their data to anticipate bioterrorism events.

However, in developing countries where this system has recently been developed, it has shown that these systems are emergency–based surveillance in the early stages of creation, and, over time, they enhance and expand their data resource.

It can also be concluded that, due to ownership, the subsystems of Bioterrorism Information System have different legal and security requirements. RODS, as the provider of a bioterrorism information system operating under the control of the army, has much stricter security requirements.

- It is suggested that various data sources be used in designing the National Bioterrorism Information System. Equipping the system with biosensors and biological detectors as well as using information related to the threats of bioterrorism attacks obtained from security and intelligence organizations have led to a real and accurate detection of bioterrorism attacks. In addition, the use of clinical and non-clinical data and technologies such as FACTS in designing will increase the accuracy and reduce the redundancy of data and finally will enhance the performance of this system.

- To design the National Bioterrorism Information System, localization in the classification of biological agents based on the demographic and epidemiological features of a country should be considered.

- It is recommended that advanced and flexible statistical methods be used at data processing phase. Geographic features of the region, epidemic diseases, demographic characteristics, classification system selection, determination of syndrome groups, and attention to the season and time of the event are significant points in order to determine threshold in data processing phase.

- Determining alert system in the design of Bioterrorism Information System depends on the security policies of each country, the extent and the impact of the bioterrorism event. Therefore, it is recommended to use different alert and notification systems based on end-user levels. Dashboard system for high-level managers, colorcoded alerts system for the public (red, orange, yellow, blue and green for severe, high, elevated, guarded to low) and email or telephone notification system for epidemiologists.

- Any possible threat or attack on this system, such as unauthorized access to the network and destruction of data, should be considered. Therefore, it is recommended to follow international and national infrastructure security guidelines during the development and implementation phase in designing Bioterrorism Information System.

¹FSIS Automated Corporate Technology Suite (FACTS)

²Statistical Process Control

³Electronic surveillance system (ISS)

⁴National Bioterrorism Syndromic Surveillance Demonstration Program

⁵Lightweight Epidemiology Advanced Detection and Emergency Response System

⁶Integrated Disease Surveillance Project

⁷FSIS Automated Corporate Technology Suite (FACTS)

⁸Secure Socket Layer

⁹Pandemic and All-Hazards PreparednessAct (PAHPA)

¹⁰NHS Direct Syndromic Surveillance system

¹¹National Bioterrorism Syndromic Surveillance Demonstration Program